Important Safety Information
Contraindications
IXEMPRA is contraindicated in patients:
- with a known history of a severe (CTC grade 3/4) hypersensitivity reaction to agents containing Cremophor® EL or its derivatives such as polyoxyethylated castor oil
- who have a baseline neutrophil count <1500 cells/mm3 or a platelet count <100,000 cells/mm3
- IXEMPRA in combination with capecitabine is contraindicated in patients with AST or ALT >2.5 x ULN or bilirubin >1 x ULN
WARNING AND PRECAUTIONS:
Toxicity in patients with hepatic impairment
- In combination with capecitabine, the overall frequency of grade 3/4 adverse reactions, febrile neutropenia, serious adverse reactions, and toxicity-related deaths was greater in patients with hepatic impairment
- IXEMPRA in combination with capecitabine is contraindicated in patients with AST or ALT >2.5 ULN or bilirubin >1 x ULN due to increased risk of toxicity- and neutropenia-related death
- Use of IXEMPRA in patients with AST or ALT >10 × ULN or bilirubin >3 × ULN is not recommended
- When using IXEMPRA as a single agent, grade 4 neutropenia, febrile neutropenia, and serious adverse reactions were more frequent in patients with hepatic impairment
- Reduce the dose of IXEMPRA based on the degree of hepatic impairment.
Peripheral neuropathy
- Peripheral neuropathy was common. Patients treated with IXEMPRA should be monitored for symptoms of neuropathy, such as burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, or neuropathic pain
- Neuropathy occurred early during treatment; ~75% of new onset or worsening neuropathy occurred during the first 3 cycles. Patients experiencing new or worsening peripheral neuropathy may require changes in the dose or discontinuation of IXEMPRA
- Neuropathy was the most frequent cause of treatment discontinuation due to drug toxicity. Caution should be used when treating patients with diabetes mellitus or preexisting peripheral neuropathy
- Withhold, reduce, or discontinue IXEMPRA depending on the severity and persistence of peripheral neuropathy
Myelosuppression
- Severe, life threatening, or fatal myelosuppression can occur in patients treated with IXEMPRA.
- Myelosuppression is dose-dependent and primarily manifested as neutropenia
- Patients should be monitored for myelosuppression; frequent peripheral blood cell counts are recommended for all patients receiving IXEMPRA
- Patients who experience severe neutropenia or thrombocytopenia should have their dose withheld, reduced or discontinued depending on the severity and persistence of myelosuppression.
- The rate of neutropenia-related deaths was higher (29%, 5 out of 17) in patients with AST or ALT >2.5 x ULN or bilirubin >1.5 x ULN
- Neutropenia-related deaths occurred in 1.9% of 414 patients with normal hepatic function or mild hepatic impairment treated with IXEMPRA in combination with capecitabine. Neutropenia-related death occurred in 0.4% of 240 patients with IXEMPRA as a single agent
Hypersensitivity reactions
- Premedicate with an H1 and an H2 antagonist approximately 1 hour before IXEMPRA infusion and observe for hypersensitivity reactions (eg, flushing, rash, dyspnea, and bronchospasm)
- In case of severe hypersensitivity reactions, infusion of IXEMPRA should be stopped and aggressive supportive treatment (eg, epinephrine, corticosteroids) started as clinically indicated.
- Patients who experience a hypersensitivity reaction in one cycle of IXEMPRA must be premedicated in subsequent cycles with a corticosteroid in addition to the H1 and H2 antagonists, and extension of the infusion time should be considered
Cardiac adverse reactions
- Caution should be exercised in patients with a history of cardiac disease. Discontinuation of IXEMPRA should be considered in patients who develop cardiac ischemia or impaired cardiac function due to reports of cardiovascular adverse reactions (eg, myocardial ischemia, supraventricular arrhythmia, and ventricular dysfunction). The frequency of cardiac adverse reactions (myocardial ischemia and ventricular dysfunction) was higher in the IXEMPRA in combination with capecitabine (1.9%) than in the capecitabine single agent (0.3%) treatment group
Pregnancy
- IXEMPRA can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential and pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IXEMPRA and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with IXEMPRA and for 4 months after the last dose.
Lactation
- Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with IXEMPRA and for 2 weeks after the last dose.
Alcohol Content
- The alcohol content in a dose of IXEMPRA may affect the central nervous system. This may include impairment of a patient's ability to drive or use machines immediately after infusion.
Adverse reactions
Single-agent
- The most common adverse reactions (≥20%) reported by patients receiving IXEMPRA single agent were peripheral sensory neuropathy, 62% (grade 3/4: 14%); fatigue/asthenia, 56% (grade 3/4: 13%); myalgia/arthralgia, 49% (grade 3/4: 8%); alopecia, 48% (grade 3/4: 0%); nausea, 42% (grade 3/4: 2%); stomatitis/mucositis, 29% (grade 3/4: 6%); vomiting, 29% (grade 3/4: 1%); diarrhea, 22% (grade 3/4: 1%); and musculoskeletal pain, 20% (grade 3/4: 3%). Drug-associated hematologic abnormalities (>40%) included neutropenia, leukopenia, anemia, and thrombocytopenia. Grade 3/4 hematologic adverse reactions included neutropenia, 54%; leukopenia, 49%; anemia, 8%; and thrombocytopenia, 7%
Combination with capecitabine
- The most common adverse reactions (≥20%) reported by patients receiving IXEMPRA in combination with capecitabine compared to capecitabine alone, respectively, were peripheral sensory neuropathy, 65% vs. 16% (grade 3/4: 21% vs. 0%); palmar-plantar erythrodysesthesia (hand-foot) syndrome, 64% vs. 63% (grade 3/4: 18% vs. 17%); fatigue/asthenia, 60% vs. 29% (grade 3/4: 16% vs. 4%); nausea, 53% vs. 40% (grade 3/4: 3% vs. 2%); diarrhea, 44% vs. 39% (grade 3/4: 6% vs. 9%); vomiting, 39% vs. 24% (grade 3/4: 4% vs. 2%); myalgia/arthralgia, 39% vs. 5% (grade 3/4: 8% vs. <1%); anorexia, 34% vs. 15% (grade 3/4: 3% vs. 1%); stomatitis/mucositis, 31% vs. 20% (grade 3/4: 4% vs. 3%); alopecia, 31% vs. 3% (grade 3/4: 0% vs. 0%); abdominal pain, 24% vs. 14% (grade 3/4: 2% vs. 1%); nail disorder, 24% vs. 10% (grade 3/4: 2% vs. <1%); musculoskeletal pain, 23% vs. 5% (grade 3/4: 2% vs. 0%); and constipation, 22% vs. 6% (grade 3/4: 0% vs. <1%).
- Drug-associated hematologic abnormalities (>40%) with IXEMPRA in combination with capecitabine and capecitabine alone, respectively, included neutropenia, leukopenia, anemia, and thrombocytopenia. Grade 3/4 hematologic adverse reactions included neutropenia, 68% vs. 11%; leukopenia, 57% vs. 6%; anemia, 10% vs. 5%; and thrombocytopenia, 8% vs. 4%
Cremophor is a registered trademark of BASF AG.
AST = aspartate aminotransferase; ALT = alanine aminotransferase; ULN = upper limit of normal; CTC = common terminology criteria.
Indications
IXEMPRA® (ixabepilone) is indicated for treatment in combination with capecitabine for patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.
- Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting
- Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting
IXEMPRA is indicated for treatment as a single agent for patients with metastatic or locally advanced breast cancer after failure of an anthracyclines, taxanes, and capecitabine.
Please see US Full Prescribing Information, including boxed WARNING regarding hepatic impairment.
Medical information
For product information or to report an adverse reaction, please call 1-844-586-8953 or e mail DrugSafety@propharmagroup.com.
This site is intended for US healthcare professionals.
The R-Pharm US Access and Support logo is a trademark and IXEMPRA® is a registered trademark of R-Pharm US Operating LLC, a wholly-owned subsidiary of R-Pharm US LLC.
© 2024, R-PHARM US. All rights reserved. IXE-00096-02 08/16
