INDICATION
JEVTANA is a microtubule inhibitor indicated in combination
with prednisone for treatment of patients with metastatic
castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen.
IMPORTANT SAFETY INFORMATION
WARNING: NEUTROPENIA AND HYPERSENSITIVITY
Neutropenia: Neutropenic deaths have been reported. Monitor for neutropenia with
frequent blood cell counts. JEVTANA is
contraindicated in patients with neutrophil counts of ≤1,500 cells/mm3. Primary prophylaxis
with G-CSF is recommended in
patients with high-risk clinical features. Consider primary prophylaxis with G-CSF in all patients
receiving a dose of
25 mg/m2.
Severe hypersensitivity: Severe hypersensitivity reactions can occur and may include
generalized rash/erythema,
hypotension and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of
the JEVTANA
infusion and administration of appropriate therapy. Patients should receive premedication. JEVTANA is
contraindicated in
patients who have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs
formulated with
polysorbate 80.
CONTRAINDICATIONS
JEVTANA is contraindicated in patients with neutrophil counts of ≤1,500/mm3, patients with a
history of severe
hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80, and patients with
severe
hepatic impairment (total bilirubin >3x upper limit of normal (ULN)).
WARNINGS AND PRECAUTIONS
Bone Marrow Suppression (BMS): BMS manifested as neutropenia, anemia, thrombocytopenia
and/or pancytopenia may occur.
Neutropenic deaths have been reported. Monitor blood counts frequently to determine if initiation of G-CSF
and/or dosage
modification is needed. Monitoring of complete blood counts is essential on a weekly basis during cycle 1 and
before
each treatment cycle thereafter so that the dose can be adjusted, if needed. Caution is recommended in
patients with
hemoglobin <10 g/dl.
Increased Toxicities in Elderly Patients: Patients ≥65 years of age were more likely to
experience fatal outcomes not
related to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia.
Monitor
closely.
Hypersensitivity Reactions: Severe hypersensitivity reactions can occur. Premedicate all
patients with antihistamines,
corticosteroids and H2 antagonists prior to JEVTANA. Observe patients closely, especially during
the first and second
infusions. Discontinue JEVTANA immediately if severe hypersensitivity occurs and treat as indicated.
Gastrointestinal (GI) Adverse Reactions: Nausea, vomiting, and severe diarrhea may occur.
Death related to diarrhea and
electrolyte imbalance occurred in the randomized clinical trials and mortality related to diarrhea has been
reported.
Intensive measures may be required for severe diarrhea and electrolyte imbalance. Rehydrate and treat with
antiemetics
and antidiarrheals as needed. If experiencing grade ≥3 diarrhea, dosage should be modified.
GI hemorrhage and perforation, ileus, enterocolitis, neutropenic enterocolitis, including fatal outcome, have
been
reported. Risk may be increased with neutropenia, age, steroid use, concomitant use of NSAIDs, antiplatelet
therapy or
anticoagulants, and prior history of pelvic radiotherapy, adhesions, ulceration and GI bleeding. Abdominal
pain and
tenderness, fever, persistent constipation, diarrhea, with or without neutropenia, may be early manifestations
of
serious GI toxicity and should be evaluated and treated promptly. JEVTANA treatment delay or discontinuation
may be
necessary.
Renal Failure: Cases, including those with fatal outcomes, have been reported. Identify
cause and manage aggressively.
Urinary Disorders including Cystitis: Cystitis, radiation cystitis, and hematuria, including
that requiring
hospitalization, has been reported with JEVTANA in patients who previously received pelvic radiation. Cystitis
from
radiation recall may occur late in treatment with JEVTANA. Monitor patients who previously received pelvic
radiation for
signs and symptoms of cystitis while on JEVTANA. Interrupt or discontinue JEVTANA in patients experiencing
severe
hemorrhagic cystitis. Medical and/or surgical supportive treatment may be required to treat severe hemorrhagic
cystitis.
Respiratory Disorders: Interstitial pneumonia/pneumonitis, interstitial lung disease and
acute respiratory distress
syndrome have been reported and may be associated with fatal outcome. Patients with underlying lung disease
may be at
higher risk for these events. Acute respiratory distress syndrome may occur in the setting of infection.
Interrupt
JEVTANA if new or worsening pulmonary symptoms develop. Closely monitor, promptly investigate, and
appropriately treat
patients receiving JEVTANA. Consider discontinuation. The benefit of resuming JEVTANA treatment must be
carefully
evaluated.
Use in Patients with Hepatic Impairment: JEVTANA dose should be reduced for patients with
mild (total bilirubin > 1 to ≤
1.5 x ULN or AST > 1.5 x ULN) and moderate (total bilirubin > 1.5 to ≤ 3.0 x ULN and any AST) hepatic
impairment, based
on tolerability data in these patients. Administer JEVTANA 20 mg/m2 for mild hepatic impairment.
Administer JEVTANA 15
mg/m2 for moderate hepatic impairment. Monitor closely.
Embryo-Fetal Toxicity: JEVTANA can cause fetal harm and loss of pregnancy. Advise males with
female partners of
reproductive potential to use effective contraception during treatment and for 4 months after the last dose of
JEVTANA.
ADVERSE REACTIONS (ARs)
The most common all grades adverse reactions and laboratory abnormalities (≥10%) with JEVTANA 20
mg/m2 or 25 mg/m2 are
neutropenia, anemia, diarrhea, nausea, fatigue, asthenia, vomiting, hematuria, constipation, decreased
appetite, back
pain, and abdominal pain.
DRUG INTERACTIONS
Avoid coadministration of JEVTANA with strong CYP3A inhibitors. If patients require coadministration of a
strong CYP3A
inhibitor, consider a 25% JEVTANA dose reduction.
USE IN SPECIFIC POPULATIONS
- Pregnancy: The safety and efficacy of JEVTANA have not been established in females.
There are no human data on the use
of JEVTANA in pregnant women to inform the drug-associated risk.
- Lactation: The safety and efficacy of JEVTANA have not been established in females.
There is no information available on
the presence of JEVTANA in human milk, the effects of the drug on the breastfed infant, or the effects of
the drug on
milk production.
- Females and Males of Reproductive Potential: Advise male patients with female
partners of reproductive potential to use
effective contraception during treatment and for 4 months after the last dose of JEVTANA.
Please see full Prescribing Information, including Boxed WARNING.
