cabazitaxel

cabazitaxel

Jevtana

Pharmacologic class: Taxane

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Neutropenic deaths have been reported. Obtain frequent blood counts to monitor for neutropenia. Don't give drug if neutrophil count is 1,500 cells/mm3 or less.

• Severe hypersensitivity can occur and may include generalized rash, erythema, hypotension, and bronchospasm. Discontinue drug immediately if severe reactions occur and administer appropriate therapy.

• Drug is contraindicated in patients with history of severe hypersensitivity reactions to cabazitaxel or to drugs formulated with polysorbate 80.

Action

As a microtubule inhibitor, cabazitaxel binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the inhibition of mitotic and interphase cellular functions.

Availability

Injection: 60 mg/1.5 ml in single-use vial

Indications and dosages

Metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing treatment regimen

Adults: 25 mg/m2 I.V. by 1-hour infusion q 3 weeks in combination with prednisone 10 mg P.O. daily throughout treatment

Dosage adjustment

• Grade 3 or greater neutropenia for longer than 1 week despite appropriate treatment, including granulocytecolony stimulating factor (G-CSF)
• Febrile neutropenia
• Grade 3 or greater diarrhea or persisting diarrhea despite appropriate treatment

Contraindications

• Hypersensitivity to drug or to other drugs formulated with polysorbate 80
• Patients with neutrophil counts of 1,500 cells/mm3 or less

Precautions

Use cautiously in:
• hepatic impairment with total bilirubin at or above the upper limit of normal (ULN), or AST or ALT levels 1.5 × ULN or greater (avoid use)
• severe renal impairment (creatinine clearance less than 30 mL/minute) and end-stage renal disease
• neutropenia
• GI symptoms
• infusion reactions
• concurrent use of strong CYP3A inducers or inhibitors (avoid use)
• elderly patients
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Follow facility policy for handling, preparing, and administering carcinogenic, mutagenic, and teratogenic drugs.

Don't administer by I.V. push or bolus.
• Premedicate patient at least 30 minutes before each dose with the following I.V. drugs to reduce risk or severity of hypersensitivity: Antihistamine (dexchlorpheniramine 5 mg, or diphenhydramine 25 mg, or equivalent antihistamine), corticosteroid (dexamethasone 8 mg or equivalent steroid), H2 antagonist (ranitidine 50 mg or equivalent H2 antagonist).
• Give oral or I.V. antiemetic prophylaxis as needed.
• Don't use PVC infusion containers or polyurethane infusion sets for preparation or administration of drug.
• Be aware that drug requires two dilutions before administering.
• To reconstitute, use entire contents of accompanying diluent to achieve a concentration of 10 mg/ml. Withdraw only required amount of first dilution to prepare final infusion solution before administering. When transferring diluent, direct needle onto inside wall of vial and inject slowly to limit foaming. Remove syringe and needle and gently mix initial diluted solution by repeated inversions for at least 45 seconds to ensure full mixing of drug and diluent. Don't shake. Let solution stand for a few minutes to allow foam to dissipate; check that solution is homogeneous and contains no visible particulate matter.
• The second dilution should be done immediately (within 30 minutes) to obtain final infusion. Withdraw recommended dose from vial containing 10 mg/ml using calibrated syringe and further dilute into sterile 250-ml PVC-free container of either normal saline solution or 5% dextrose solution for infusion. If dose greater than 65 mg is required, use larger volume of infusion vehicle so that a concentration of 0.26 mg/ml isn't exceeded. Concentration of final infusion solution should be between 0.10 and 0.26 mg/ml. Remove syringe and thoroughly mix final infusion solution by gently inverting bag or bottle. Final infusion solution in either normal saline solution or 5% dextrose solution should be used within 8 hours if kept at ambient temperature (including the 1-hour infusion) or within a total of 24 hours if refrigerated (including the 1-hour infusion).
• Inspect visually for particulate matter, crystals, and discoloration before administering. Discard unused portion.
• Discard first diluted solution or second (final) infusion solution if either isn't clear or appears to have precipitation.
• As final infusion solution is supersaturated, it may crystallize over time. If this occurs, don't use solution; discard it.
• Don't mix with other drugs.
• Use an in-line filter of 0.22-micrometer nominal pore size for administration.

Reduce dosage as prescribed for Grade 3 or greater neutropenia lasting longer than 1 week despite appropriate treatment (including G-CSF), for febrile neutropenia, or for Grade 3 or greater diarrhea or persisting diarrhea despite appropriate treatment. Discontinue drug if patient continues to experience any of these reactions at prescribed lower dosage.
• Consider G-CSF and secondary prophylaxis in all patients considered to be at increased risk for neutropenia complications.

Immediately discontinue infusion if severe hypersensitivity reactions occur and initiate appropriate therapy. Be aware that patients with a history of severe hypersensitivity reactions shouldn't be rechallenged with this drug.

Adverse reactions

CNS: headache, dizziness, asthenia, fatigue, peripheral neuropathy

CV: hypotension, arrhythmia

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, anorexia, dyspepsia, mucosal inflammation

GU: hematuria, urinary tract infection, dysuria, renal failure

Hematologic: neutropenia, anemia, leukopenia, thrombocytopenia

Musculoskeletal: back pain, arthralgia, muscle spasms

Respiratory: dyspnea, cough

Skin: alopecia

Other: pyrexia, dysgeusia, pain, weight loss, dehydration, peripheral edema,

hypersensitivity

Interactions

Drug-drug.Strong CYP3A inducers (such as carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin): decreased cabazitaxel concentration

Strong CYP3A inhibitors (such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole): increased cabazitaxel concentration

Drug-diagnostic tests. ALT, AST, bilirubin: increased levels

Drug-herbs. St. John's wort: decreased cabazitaxel concentration

Patient monitoring

• Monitor CBC with differential and renal and hepatic function tests closely.
• Be aware that the incidence of Grade 3 to 4 hematologic adverse reactions, particularly neutropenia and febrile neutropenia, is higher in patients age 65 or older compared to younger patients.

Be aware that cabazitaxel is extensively metabolized in the liver and hepatic impairment is likely to increase cabazitaxel concentration, with risk of severe and life-threatening complications in patients receiving other drugs belonging to same class.

Continue to closely monitor patents for hypersensitivity reactions, especially during first and second infusions. Hypersensitivity reactions may occur within a few minutes after initiation of infusion; therefore, have facilities and equipment available for treatment of hypotension and bronchospasm. If severe hypersensitivity occurs that includes generalized rash, erythema, hypotension, and bronchospasm, immediately discontinue infusion and initiate appropriate therapy.
• Watch for dehydration if patient has nausea, vomiting, or severe diarrhea; be aware that intensive measures may be required for severe diarrhea and electrolyte imbalance. Initite appropriate measures, including rehydration and antidiarrheal or antiemetic medications, as needed. Delay or reduce dosage as necessary if patient has diarrhea at or above Grade 3.

Be aware that renal failure may occur in association with sepsis, dehydration, or obstructive uropathy. Immediately take appropriate measures to identify causes of renal failure and treat aggressively.

Patient teaching

• Explain the importance of taking oral prednisone as prescribed.
• Explain the importance of routine blood cell counts and instruct patient to monitor temperature frequently.

Instruct patient to immediately contact prescriber if signs and symptoms of hypersensitivity reactions occur, including rash or itching, skin redness, dizziness or faintness, chest or throat tightness, facial swelling, or breathing problems.

Instruct patient to immediately contact prescriber if urinary tract problems, irregular heartbeat, significant vomiting or diarrhea, decreased urinary output, or blood in urine occurs.
• Advise patient to report numbness or tingling of the hands or feet or muscle problems.
• Advise patient to contact prescriber if a fever or other evidence of potential infection, such as cough or pain on urination, develops.
• Instruct patient to tell prescriber all drugs he's taking, because some drugs have potential for serious drug interactions and shouldn't be taken with cabazitaxel.
• Advise patient not to use St. John's wort without consulting prescriber.
• Advise female patient of childbearing age to avoid becoming pregnant while receiving this drug.
• Advise breastfeeding patient that she should decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of drug for her treatment.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.

cabazitaxel

(ka-ba-zi-tax-el) ,

Jevtana

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: taxoids
Pregnancy Category: D

Indications

Hormone-refractory metastatic prostate cancer previously treated with a regimen including docetaxel (used in combination with prednisone).

Action

Binds to intracellular tubulin and promotes its assembly into microtubules while inhibiting disassembly. Result is inhibition of mitotis and interphase.

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones, with ↓ spread of metastatic prostate cancer.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Equally distributed between blood and plasma.
Metabolism and Excretion: Extensively (>95%) metabolized by the liver, 80–90% by CYP3A4/5 enzyme system. Metabolites are excreted in urine and feces. Minimal renal excretion.
Half-life: Terminal elimination—95 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
IVrapidend of infusionunknown

Contraindications/Precautions

Contraindicated in: Severe hypersensitivity to cabazitaxel or polysorbate 80;Neutrophils ≤1,500/mm3;Hepatic impairment (total bilirubin ≥upper limits of normal, or AST and/or ALT ≥1.5 × upper limits of normal);Concurrent use of strong CYP3A4 inhibitors, inducers and St. John's wort; Obstetric: Avoid use during pregnancy (may cause fetal harm); Lactation: Breast feeding should be avoided.
Use Cautiously in: Concurrent use of moderate CYP3A4 inhibitors; Obstetric: Patients with childbearing potential (pregnancy should be avoided);Patients with severe renal impairment (CCr <30 mL/min) or end-stage renal disease; Geriatric: Patients >65 yr ↑ risk of adverse reactions; Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • weakness (most frequent)
  • fatigue

Respiratory

  • dyspnea (most frequent)

Cardiovascular

  • arrhythmias
  • hypotension

Gastrointestinal

  • diarrhea
  • abdominal pain (most frequent)
  • abnormal taste (most frequent)
  • anorexia (most frequent)
  • constipation (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • dyspepsia

Genitourinary

  • renal failure (life-threatening)
  • hematuria (most frequent)

Dermatologic

  • alopecia (most frequent)

Fluid and Electrolyte

  • electrolyte imbalance

Hematologic

  • neutropenia
  • thrombocytopenia
  • anemia (most frequent)
  • leukopenia (most frequent)

Musculoskeletal

  • arthralgia (most frequent)
  • back pain (most frequent)
  • muscle spasms

Neurologic

  • peripheral neuropathy (most frequent)

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • fever (most frequent)

Interactions

Drug-Drug interaction

Concomitant administration of strong CYP3A inhibitors including ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole ↑ levels and risk of toxicity and should be avoided.Concomitant administration of strong CYP3A inducers including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, and phenobarbital may ↓ levels and effectiveness and should be avoided.St. John's wort may ↓ levels and effectiveness and should be avoided.

Route/Dosage

Oral (Adults) 25 mg/m2 every 3 wk as a 1-hr infusion (with prednisone 10 mg PO daily).

Availability

Viscous solution for injection (requires two dilutions prior to IV administration): 60 mg/1.5 mL (contains polysorbate 80) comes with diluent (5.7 mL of 13% [w/w] ethanol in water for injection)

Nursing implications

Nursing assessment

  • Assess for hypersensitivity reactions (generalized rash/erythema, hypotension, bronchospasm, swelling of face). May occur within minutes following initiation of infusion. If severe reactions occur, discontinue infusion immediately and provide supportive therapy.
  • Assess for nausea, vomiting, and severe diarrhea; may result in death due to electrolyte imbalance. Premedication is recommended. Treat with rehydration, anti-diarrheal, or antiemetic therapy as needed. If Grade ≥3 diarrhea or persisting diarrhea occurs despite appropriate medication, fluid and electrolyte replacement, delay treatment until improvement or resolution, then reduce dose to 20 mg/mL.
  • Lab Test Considerations: Monitor CBC weekly during cycle 1 and before each treatment cycle thereafter. Do not administer if neutrophils ≤1500/mm3. If prolonged grade 3 neutropenia (>1 wk) despite appropriate medication including filgrastim, delay treatment until neutrophil count is >1500 mm3, then reduce dose to 20 mg/m2. Use filgrastim for secondary prophylaxis.
    • If febrile neutropenia occurs, delay therapy until improvement or resolution and neutrophil count is >1500/mm3, then reduce dose to 20 mg/m2. Use filgrastim for secondary prophylaxis.
    • Discontinue cabazitaxel if prolonged Grade 3 neutropenia, febrile neutropenia, or Grade 3 diarrhea occur at the 20 mg/m2 dose.
    • May cause hematuria.
    • May cause Grade 3–4 ↑ AST, ↑ ALT, and ↑ bilirubin.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • high alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order and dose calculations.
  • Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers. If solution comes in contact with skin or mucosa, wash with soap and water immediately.
  • Premedicate at least 30 min before each dose with antihistamine (diphenhydramine 25 mg or equivalent), corticosteroid (dexamethasone 8 mg or equivalent), and H2 antagonist (ranitidine 50 mg or equivalent). Antiemetic prophylaxis, PO or IV, is recommended.
  • Intravenous Administration
  • pH: No data.
  • Two dilutions are required. Do not use PVC infusion containers or polyurethane infusion sets for preparation or infusion.
    • First Dilution:Diluent: Mix vial with entire contents of supplied diluent. Direct needle to inside wall id vial and inject slowly to avoid foaming. Mix gently by repeated inversions for at least 45 sec; do not shake. Let stand for a few minutes to allow foam to dissipate.Concentration: 10 mg/mL.
    • Second Dilution:Diluent: Withdraw recommended dose from cabazitaxel solution and dilute further into a setrile 250 mL PVC-free container of 0.9% NaCl or D5W. If dose >65 mg is required, use a larger volume of infusion vehicle so concentration does not exceed 0.26 mg/mL. Gently invert container to mix.Concentration: 0.10–0.26 mg/mL. Stable for 8 hr (including 1 hr infusion) at room temperature or 24 hr if refrigerated. May crystalize over time. Do not use if crystalized, discolored, or contains particulate matter; discard.
  • Rate: Infuse over 1 hr at room temperature through a 0.22 micrometer nominal pore size filter.
  • Y-Site Incompatibility: Do not mix with other medication.

Patient/Family Teaching

  • Instruct patient to take oral prednisone as prescribed and to notify health care professional if a dose is missed or not taken in time.
  • Advise patient to notify health care professional immediately if signs or symptoms of hypersensitivity reactions; fever; sore throat; signs of infection; lower back or side pain; difficult or painful urination; sores on the mouth or on the lips; bleeding gums; bruising; petechiae; blood in urine, stool, or emesis; unusual swelling occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should also be cautioned not to drink alcoholic beverages or to take products containing aspirin or NSAIDs; may precipitate GI hemorrhage.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Advise female patients of the need for contraception and to avoid breast feeding during therapy.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Emphasize need for periodic lab tests to monitor for side effects. Advise patient to monitor temperature frequently.

Evaluation/Desired Outcomes

  • ↓ in size and spread of metastatic prostate cancer.
References in periodicals archive ?
1, ATC code: L01CD04, Generic Name: Cabazitaxel, Pharmaceutical form: Conc.
AFFINITY is designed to evaluate whether the investigational treatment custirsen, when combined with cabazitaxel, improves survival in men with metastatic castrate-resistant prostate cancer (CRPC) whose disease has progressed following treatment with docetaxel.
In subgroup analyses, the only group who showed a significant difference in favor of cabozantinib were those who had previously been treated with cabazitaxel (n = 393).
Sanofi announced today that it has reached agreement with NHS England that cabazitaxel will once more be available on the NHS to clinically eligible men with advanced prostate cancer.
Despite the fund being boosted to PS340 million in April, 25 of the 84 drug treatments currently available will be stopped, including prostate cancer drug cabazitaxel.
These drugs are Degarelix, Abiraterone acetate, Plerixafor, Eribulin mesylate, Mucotrol, Crizotinib, Etravirine, Nelarabine, Fingolimod, Tolvaptan, Rilpivirine, Vemurafenib, Lipiodol UF, Cabazitaxel and Panitumumab.
In 2010, the autologous cellular immunotherapy sipuleucel-T (Provenge; Dendreon) (5) and the novel taxane cabazitaxel (Jevtana; Sanofi-Aventis) (6) were shown to prolong survival significantly and were subsequently approved by the US Food and Drug Administration (FDA).
The Institute of Cancer Research, London, and its partner hospital The Royal Marsden NHS Foundation Trust jointly led the new Phase III trial of enzalutamide and the Phase III trials of two other drugs, cabazitaxel and abiraterone.
Cabazitaxel, which is marketed as Jevtana, can extends the life of late-stage patients by an average of three months.
The National Institute for Health and Clinical Excellence (Nice) has upheld its decision not to approve the drug cabazitaxel, also known as Jevtana.
The National Institute for Health and Clinical Excellence (Nice) said cabazitaxel (Jevtana), in combination with prednisone or prednisolone was not cost-effective as a second line treatment after hormone therapy.
But the body also considered the drug, cabazitaxel, was not cost effective in comparison with other treatments.