Dosing and Administration | JEVTANA® (cabazitaxel) Injection
`
`WARNING: NEUTROPENIA AND HYPERSENSITIVITY
`• Neutropenic deaths have been reported. In order to monitor the occurrence of neutropenia, frequent blood cell counts
`should be performed on all patients receiving JEVTANA . JEVTANA is contraindicated in patients with neutrophil
`®
`®
`counts of ≤1,500 cells/mm . [...]
`3
`View Full Important Safety Information 
`
`For U.S. Healthcare Professionals Only
`
`For Patients 
`
`Full Prescribing Information including Boxed WARNING 
`
`ABOUT JEVTANA
`®
`
`PHASE III TROPIC TRIAL WHEN TO INITIATE JEVTANA
`®
`
`SAFETY PROFILE
`
`DOSING AND ADMINISTRATION
`
`RESOURCES
`
`PREMEDICATION
`
`DOSING
`
`PREPARATION AND ADMINISTRATION
`
`Home  Dosing and Administration  Dosing
`
`Dosing
`Dosing and Administration
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`1
`
`Dosing schedule
`For patients with hormone-refractory metastatic prostate cancer previously treated with a
`docetaxel-containing regimen:
`
`JEVTANA 25 mg/m as a 1-hour IV infusion
`®
`2
`every 3 weeks
`+ oral predisone 10 mg daily throughout treatment
`
`Dose modifications
`
`1
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`Toxicity
`
`Dose modification
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`Prolonged grade ≥3 neutropenia
`a
`(>1 week) despite appropriate
`medication including granulocyte-
`colony stimulating factor (G-CSF)
`
`Delay treatment until neutrophil count is >1,500 cells/mm
`then reduce dosage of JEVTANA to 20 mg/m . Use
`®
`2
`granulocyte-colony stimulating factor (G-CSF) for secondary
`prophylaxis.
`
`3
`
`,
`
`Febrile neutropenia or neutropenic
`infection
`
`Grade ≥3 diarrhea or persisting
`diarrhea despite appropriate
`medication, fluid and electrolyte
`replacement
`
`Delay treatment until improvement or resolution, and until
`neutrophil count is >1,500 cells/mm , then reduce dosage of
`3
`JEVTANA to 20 mg/m . Use granulocyte-colony stimulating
`2
`factor (G-CSF) for secondary prophylaxis.
`
`Delay treatment until improvement or resolution, then reduce
`dosage of JEVTANA to 20 mg/m .
`®
`2
`
`Grade 2 peripheral neuropathy
`
`Delay treatment until improvement or resolution, then reduce
`2
`
`http://jevtana.com/hcp/dosing/default.aspx[6/28/2016 5:42:02 PM]
`
`Important Safety Information for
`JEVTANA (cabazitaxel) injection
`®
`
`•
`
`WARNING: NEUTROPENIA
`AND HYPERSENSITIVITY
`Neutropenic deaths have been
`•
`reported. In order to monitor the
`occurrence of neutropenia, frequent
`blood cell counts should be performed on
`all patients receiving JEVTANA .
`®
`JEVTANA is contraindicated in patients
`®
`with neutrophil counts of ≤1,500
`cells/mm .
`3
`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.
`
`•
`
`Continue 
`
`JEVTANA is a microtubule inhibitor
`®
`indicated in combination with
`prednisone for the treatment of
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`MYLAN PHARMS. INC. EXHIBIT 1049 PAGE 1
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`Dosing and Administration | JEVTANA® (cabazitaxel) Injection
`
`Grade ≥3 peripheral neuropathy
`
`Discontinue JEVTANA.
`
`dosage of JEVTANA to 20 mg/m .
`
`patients with hormone-refractory
`metastatic prostate cancer (mHRPC)
`previously treated with a docetaxel-
`containing treatment regimen.
`
`9
`
`a
`
`•
`
`•
`
`/L.
` Absolute neutrophil count <1.0 x 10
`Discontinue JEVTANA treatment if a patient continues to experience any of these
`•
`®
`reactions at the 20 mg/m dosage
`2
`Dose reductions were reported in 12% of JEVTANA
`mitoxantrone-treated patients
`Dose delays were reported in 28% of JEVTANA
`mitoxantrone-treated patients
`
`-treated patients and 4% of
`®
`
`®
`
`-treated patients and 15% of
`
`•
`
`•
`
`Important Safety Information for JEVTANA
`®1
`Observe patients closely for hypersensitivity reactions, especially during the first and
`second infusions.
`Severe hypersensitivity can occur and may include generalized rash/erythema,
`hypotension and bronchospasm. Discontinue JEVTANA
` immediately if severe reactions
`®
`occur and administer appropriate therapy.
`Contraindicated if history of severe hypersensitivity reactions to cabazitaxel or to drugs
`formulated with polysorbate 80.
`Nausea, vomiting and severe diarrhea, at times, may occur. Death related to diarrhea and
`electrolyte imbalance occurred in the randomized clinical trial. Intensive measures may be
`required for severe diarrhea and electrolyte imbalance.
`Females of childbearing potential should be advised to avoid becoming pregnant during
`treatment with JEVTANA.
`®
`
`•
`
`•
`
`•
`
`Important Safety Information for JEVTANA (cabazitaxel) injection
`®
`
`•
`
`WARNING: NEUTROPENIA AND HYPERSENSITIVITY
`Neutropenic deaths have been reported. In order to monitor the occurrence of neutropenia,
`•
`frequent blood cell counts should be performed on all patients receiving JEVTANA .
`®
`JEVTANA is contraindicated in patients with neutrophil counts of ≤1,500 cells/mm .
`®
`3
`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/mm
`-
`3
`history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with
`-
`polysorbate 80
`severe hepatic impairment (total bilirubin > 3 x upper limit of normal (ULN))
`
`-
`
`http://jevtana.com/hcp/dosing/default.aspx[6/28/2016 5:42:02 PM]
`
`MYLAN PHARMS. INC. EXHIBIT 1049 PAGE 2
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`

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`Dosing and Administration | JEVTANA® (cabazitaxel) Injection
`
`WARNINGS AND PRECAUTIONS
`Bone marrow suppression manifested as neutropenia, anemia, thrombocytopenia and/or
`pancytopenia may occur. Neutropenic deaths have been reported.
`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
`Monitor blood counts frequently to determine if initiation of G-CSF and/or dosage
`modification is needed
`Primary prophylaxis with G-CSF should be considered in patients with high-risk clinical
`features
`Caution is recommended in patients with hemoglobin < 10 g/dl
`
`-
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`-
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`•
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`•
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`•
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`•
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`•
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`•
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`•
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`•
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`•
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`- S
`
`-
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`- M
`
`evere hypersensitivity reactions can occur.
`Premedicate all patients with antihistamines, corticosteroids and H
`-
`initiation of the JEVTANA infusion
`®
`Observe patients closely for hypersensitivity reactions, especially during the first and
`second infusions
`Discontinue infusion immediately if severe hypersensitivity is observed and treat as
`indicated
`
`2
`
` antagonists prior to the
`
`ortality related to diarrhea has been reported.
`Rehydrate and treat with anti-emetics and anti-diarrheals as needed
`If experiencing grade ≥3 diarrhea, dosage should be modified
`
`-
`
`- N
`
`ausea, vomiting and severe diarrhea, at times, may occur. Death related to diarrhea and
`electrolyte imbalance occurred in the randomized clinical trial. Intensive measures may be
`required for severe diarrhea and electrolyte imbalance.
`Gastrointestinal (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,
`-
`anti-platelet therapy or anti-coagulants, 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, including cases with fatal outcomes, has been reported. Identify cause and
`manage aggressively.
`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.
`Patients with impaired hepatic function:
`JEVTANA® is contraindicated in patients with severe hepatic impairment (total bilirubin > 3
`-
`x ULN)
`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® with caution in patients with mild and moderate hepatic impairment
`and closely monitor for safety
`
`-
`
`-
`
`JEVTANA can cause fetal harm when administered to a pregnant woman.
`®
`JEVTANA is not indicated for use in female patients
`-
`There are no adequate and well-controlled studies in pregnant women using JEVTANA
`-
`Females of childbearing potential should be advised to avoid becoming pregnant during
`-
`treatment with JEVTANA
`®
`
`®
`
`http://jevtana.com/hcp/dosing/default.aspx[6/28/2016 5:42:02 PM]
`
`MYLAN PHARMS. INC. EXHIBIT 1049 PAGE 3
`
`

`
`Dosing and Administration | JEVTANA® (cabazitaxel) Injection
`
`•
`
`•
`
`ADVERSE REACTIONS
`Deaths due to causes other than disease progression within 30 days of last study drug dose
`were reported in 18 (5%) JEVTANA -treated patients. The most common fatal adverse
`®
`reactions in JEVTANA -treated patients were infections (n=5) and renal failure (n=4).
`®
`The most common (≥10%) grade 1-4 adverse reactions were anemia, leukopenia, neutropenia,
`thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain,
`hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia,
`and alopecia.
`The most common (≥5%) grade 3-4 adverse reactions in patients who received JEVTANA were
`®
`neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue, and asthenia.
`
`•
`
`Please see full prescribing information including boxed
`
`WARNING.
`
`Reference
`1. JEVTANA Prescribing Information. Bridgewater, NJ: sanofi-aventis U.S. LLC; June 2015.
`®
`
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`US.CAB.15.06.012 Last Update: July 2015
`
`http://jevtana.com/hcp/dosing/default.aspx[6/28/2016 5:42:02 PM]
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`MYLAN PHARMS. INC. EXHIBIT 1049 PAGE 4