Jevtana60 mg/1.5 ml

Jevtana is an antineoplastic (anticancer) taxane medicine used in oncology.

Established / FDA-approved use

• In combination with oral prednisone (or prednisolone), Jevtana is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with a docetaxel-containing chemotherapy regimen.

Important notes on use

• Jevtana is only used after prior docetaxel therapy has failed or disease has progressed; it is not a first-line treatment for prostate cancer.
• Jevtana must always be given in combination with prednisone/prednisolone as part of the approved regimen, not as monotherapy.
• There is no approved indication for Jevtana outside metastatic castration-resistant prostate cancer; use in other cancers is investigational/off-label and should only occur within a clinical trial or under specialist oncology direction.
• Jevtana must be prescribed and administered only by a qualified oncology specialist in a hospital or cancer-care facility equipped to manage severe neutropenia and infusion reactions.

Each single-use vial of Cabazitaxel concentrate for solution for infusion typically contains 60 mg of cabazitaxel per 1.5 mL (40 mg/mL), supplied as a kit together with a separate diluent vial (13% ethanol in water for injection) used for the mandatory first dilution step before further dilution in an infusion solution.

Strengths and exact pack presentations can vary slightly by manufacturer; always check the product label/leaflet dispensed for the precise concentration and diluent volume.

Jevtana is a semi-synthetic taxane, a class of anticancer drugs derived from the needles of the yew (Taxus) plant. It is chemically related to other taxanes such as docetaxel and paclitaxel but has a modified structure that allows it to remain active in tumour cells that have developed resistance to docetaxel.

Jevtana is supplied as a sterile concentrate that must be diluted before being given as a slow intravenous infusion in a hospital or specialist oncology infusion unit; it is not available as an oral tablet or capsule and is not self-administered by patients.

Jevtana belongs to the taxane class of antineoplastic (cytotoxic chemotherapy) agents, which act as microtubule inhibitors. It is used specifically in the management of metastatic castration-resistant prostate cancer.

Mechanism

Cabazitaxel works by binding to tubulin and promoting its assembly into microtubules while simultaneously inhibiting microtubule disassembly. This stabilises the microtubule network of the cell, blocking normal mitotic and interphase cellular functions, arresting cancer cells in the G2/M phase of the cell cycle, and ultimately triggering cell death (apoptosis).

Unlike some other taxanes, Cabazitaxel has low affinity for the P-glycoprotein drug efflux pump, which allows it to remain effective against tumour cells that have become resistant to docetaxel through this mechanism.

Pharmacokinetics

• Distribution: Extensive tissue distribution; high plasma protein binding (approximately 89-92%).
• Metabolism: Extensively metabolised in the liver, predominantly by the CYP3A4/5 enzyme system, with minor contribution from CYP2C8.
• Elimination: Mainly excreted in the faeces (via bile), with a smaller fraction eliminated in urine; terminal half-life is approximately 95 hours.

• Jevtana is given only as a slow intravenous infusion over approximately 1 hour, through a suitable IV line fitted with an in-line filter (0.22 micrometre), by trained oncology healthcare staff.
• It must never be given as a rapid IV push, by intramuscular or subcutaneous injection, or taken by mouth.
• Non-PVC (polyvinyl chloride) infusion containers and administration sets should be used for the final diluted solution.
• Premedication (antihistamine, corticosteroid, H2 antagonist) must be completed before the infusion starts (see Dosage and Administration).
• Patients are monitored closely during and for a period after infusion for signs of a hypersensitivity reaction; the infusion is stopped immediately if a severe reaction occurs.
• Jevtana is a cytotoxic (hazardous) drug - it must be prepared and handled using appropriate protective equipment and institutional hazardous-drug procedures.

Strong CYP3A inhibitors

Drugs such as ketoconazole, itraconazole, voriconazole, clarithromycin, and ritonavir can significantly increase blood levels of Jevtana, raising the risk of toxicity. Concomitant use should be avoided; if unavoidable, a dose reduction of Jevtana of approximately 25% should be considered under specialist guidance.

Strong CYP3A inducers

Drugs such as rifampicin, phenytoin, carbamazepine, and St John's Wort can reduce blood levels of Jevtana and potentially reduce its effectiveness. Concomitant use should generally be avoided.

Other myelosuppressive or bone-marrow-toxic drugs

Using Jevtana together with other chemotherapy agents or drugs that suppress bone marrow function can add to the risk of severe neutropenia and infection; this combination requires careful specialist monitoring (see Precautions and Warnings for the boxed neutropenia warning).

Very common (may affect more than 1 in 10 people)

Common / serious effects requiring prompt medical attention

• Febrile neutropenia (fever with a low white blood cell count) - a medical emergency, see boxed warning in Precautions.
• Hypersensitivity reactions - rash, flushing, hypotension, breathing difficulty (bronchospasm) during or shortly after infusion.
• Peripheral neuropathy - numbness, tingling, or pain in the hands or feet.
• Severe or persistent diarrhoea leading to dehydration.
• Renal (kidney) impairment, particularly with dehydration or infection.
• Cystitis or blood in the urine, especially in patients with prior pelvic radiation.
• Cough, shortness of breath, or signs of lung inflammation (interstitial lung disease/pneumonitis).

Patients should contact their treating oncology team immediately if fever, signs of infection, severe diarrhoea, breathing difficulty, or unusual bleeding/bruising occur.

Jevtana is an antineoplastic drug that can cause fetal harm and is not intended for use in women of reproductive age, as it is approved only for prostate cancer in men. However, because it affects DNA and rapidly dividing cells, men receiving Jevtana who have a partner of reproductive potential should use effective contraception during treatment and for at least 4 months after the last dose, as it may affect sperm and could theoretically cause harm to a developing fetus.

It is not known whether Jevtana passes into human breast milk; given its cytotoxic nature, it should not be used by a breastfeeding parent, and breastfeeding is not recommended during treatment. Use only under the direct guidance of an oncology specialist, and consult a physician regarding fertility and family-planning implications before starting treatment.

Boxed warning: Neutropenia

Jevtana can cause severe, life-threatening, and sometimes fatal neutropenia (low white blood cell count), including febrile neutropenia. Regular complete blood count monitoring is mandatory throughout treatment. Growth-factor (G-CSF) prophylaxis is recommended for higher-risk patients and should be considered for all patients, particularly at the 25 mg/m² dose. Treatment must not be given if the neutrophil count is below the specified safety threshold (see Contraindications).

Hypersensitivity reactions

Severe hypersensitivity reactions, including generalised rash, hypotension, and bronchospasm, can occur, most often during the first two infusions. Premedication (see Dosage and Administration) is required before every infusion, and the infusion must be stopped immediately, with supportive treatment given, if a severe reaction develops.

Gastrointestinal toxicity

Severe diarrhoea, nausea, vomiting, and, rarely, gastrointestinal haemorrhage, perforation, or neutropenic enterocolitis have been reported, occasionally with fatal outcomes, especially when combined with neutropenia and dehydration. Prompt supportive management (fluids, anti-diarrhoeal treatment) and dose modification are important.

Renal impairment

Renal failure has been reported, particularly in association with severe diarrhoea, dehydration, sepsis, or urinary obstruction; adequate hydration and prompt management of diarrhoea/infection are important preventive measures.

Urinary/bladder toxicity

Cystitis, including radiation-associated cystitis, and haematuria have been reported, more frequently in patients with a history of pelvic radiotherapy; severe haemorrhagic cystitis may require interruption or discontinuation of treatment.

Peripheral neuropathy

As with other taxane-class drugs, peripheral neuropathy can occur; dose adjustment or discontinuation may be required for moderate to severe symptoms.

Respiratory disorders

Interstitial pneumonia, pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, including fatal cases, have been reported; new or worsening respiratory symptoms should be evaluated promptly.

Specialist administration only

Jevtana requires dosing individualisation, careful monitoring, and administration by an oncology specialist with access to appropriate supportive care (including management of neutropenia, infection, and infusion reactions); it is not a medicine for outpatient self-administration.

Hazardous drug handling

Jevtana is a cytotoxic agent; preparation, handling, and disposal should follow institutional procedures for hazardous drugs.

There is no known specific antidote for Jevtana overdose. Expected effects of overdose are an exaggeration of known adverse effects, particularly severe bone marrow suppression (neutropenia), gastrointestinal toxicity (mucositis, diarrhoea), and peripheral neuropathy.

If an overdose is suspected, the patient should be transferred immediately to a hospital or specialist oncology unit for close monitoring and supportive care, including frequent blood count checks; there is no home treatment for suspected overdose. Contact emergency medical services or the nearest hospital without delay.

Store Jevtana vials at 20°C-25°C (68°F-77°F); brief excursions between 15°C-30°C are permitted during transport. Do not freeze. Protect vials from bright light by keeping them in their original outer carton until use. As a hazardous cytotoxic medicine, it should be stored, handled, and disposed of according to institutional hazardous-drug procedures, and always kept out of the reach of children. It is dispensed and stored within a hospital/oncology pharmacy setting rather than at home.

Renal impairment

No specific dose adjustment of Jevtana has been formally established for renal impairment; caution is advised, especially in moderate-to-severe impairment, and renal function should be monitored (see Precautions and Warnings for the renal-failure warning).

Hepatic impairment

Dose must be reduced in mild or moderate hepatic impairment, and Jevtana is contraindicated in severe hepatic impairment - see Dosage and Administration and Contraindications.

Elderly patients

Patients aged 65 years and older who receive Jevtana have a higher reported rate of severe neutropenia, febrile neutropenia, and overall mortality compared with younger patients; closer clinical and laboratory monitoring is recommended in this age group.

Pediatric use

Jevtana is not indicated in children; see Pediatric Uses.

Jevtana is typically given as repeated cycles every 3 weeks. Treatment is generally continued for as long as the patient continues to benefit (disease control) and tolerates the medicine, and is stopped if the disease progresses, unacceptable toxicity occurs, or the treating oncologist determines that continuing is no longer appropriate. There is no fixed maximum number of cycles; duration is individualised by the treating oncology specialist based on response, blood counts, and side effects.

Jevtana requires a mandatory two-step dilution before use, performed only by trained personnel under aseptic conditions:

1. Initial dilution: The entire contents of the supplied diluent vial are transferred into the Jevtana concentrate vial to produce an initial diluted solution of approximately 10 mg/mL. The vial is gently rotated/inverted (not shaken vigorously) to avoid foaming, and the solution is allowed to stand until any foam subsides.
2. Further dilution: The required dose of the initial diluted solution is withdrawn and further diluted into an infusion bag/bottle of 0.9% sodium chloride or 5% dextrose solution (minimum 250 mL) to achieve a final concentration between approximately 0.10 mg/mL and 0.26 mg/mL.

Non-PVC infusion containers and administration sets must be used. The final infusion solution should be used within 8 hours at room temperature (including infusion time) or within 24 hours if refrigerated (2-8°C), followed by up to 1 hour at room temperature before completing the infusion. A 0.22-micrometre in-line filter must be used during administration. Any unused solution should be discarded per hazardous-drug disposal procedures.

Cabazitaxel is classified as an antineoplastic (anticancer) agent, specifically a taxane / microtubule inhibitor, and is a semi-synthetic derivative of a natural taxoid compound.

Cabazitaxel binds to tubulin, the structural protein of microtubules, and promotes microtubule assembly while blocking their disassembly. This stabilisation of the microtubule network disrupts the normal mitotic spindle apparatus, halting cell division at the G2/M phase of the cell cycle and ultimately leading to apoptosis (programmed cell death) of the cancer cell. A key distinguishing feature of Cabazitaxel is its low affinity for the P-glycoprotein efflux transporter, allowing it to remain effective in tumour cells that have become resistant to other taxanes, such as docetaxel, through overexpression of this pump.

The safety and effectiveness of Jevtana in children and adolescents have not been established. Jevtana is approved only for metastatic castration-resistant prostate cancer, a disease that does not occur in the pediatric population, so there is no approved pediatric indication or dosing regimen. Jevtana should not be used in children outside of a formal clinical trial setting.