"The U.S. Food and Drug Administration today granted accelerated approval to Ibrance (palbociclib) to treat advanced (metastatic) breast cancer.
Breast cancer in women is the second most common type of cancer in the United States. It forms i"...
The following adverse reactions are discussed in greater detail in other sections.
- Peripheral neuropathy [see WARNINGS AND PRECAUTIONS]
- Myelosuppression [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.
Unless otherwise specified, assessment of adverse reactions is based on one randomized study (Study 046) and one single-arm study (Study 081). In Study 046, 369 patients with metastatic breast cancer were treated with IXEMPRA 40 mg/m² administered intravenously over 3 hours every 21 days, combined with capecitabine 1000 mg/m² twice daily for 2 weeks followed by a 1-week rest period. Patients treated with capecitabine as monotherapy (n=368) in this study received 1250 mg/m² twice daily for 2 weeks every 21 days. In Study 081, 126 patients with metastatic or locally advanced breast cancer were treated with IXEMPRA 40 mg/m² administered intravenously over 3 hours every 3 weeks.
The most common adverse reactions ( ≥ 20%) reported by patients receiving IXEMPRA were peripheral sensory neuropathy, fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting, stomatitis/mucositis, diarrhea, and musculoskeletal pain. The following additional reactions occurred in ≥ 20% in combination treatment: palmar-plantar erythrodysesthesia (hand-foot) syndrome, anorexia, abdominal pain, nail disorder, and constipation. The most common hematologic abnormalities ( > 40%) include neutropenia, leukopenia, anemia, and thrombocytopenia.
Table 4 presents nonhematologic adverse reactions reported in 5% or more of patients. Hematologic abnormalities are presented separately in Table 5.
Table 4: Nonhematologic Drug-related Adverse Reactions Occurring
in at Least 5% of Patients with Metastatic or Locally Advanced Breast Cancer
Treated with IXEMPRA
|System Organ Classa/Preferred Term||Study 046||Study 081|
|IXEMPRA with capecitabine n=369||Capecitabine n=368||IXEMPRA monotherapy n=126|
|Total (%)||Grade 3/4 (%)||Total (%)||Grade 3/4 (%)||Total (%)||Grade 3/4 (%)|
|Infections and Infestations|
|Upper respiratory tract infectionb||4||0||3||0||6||0|
|Blood and Lymphatic System Disorders|
|Immune System Disorders|
|Metabolism and Nutrition Disorders|
|Nervous System Disorders|
|Motor neuropathyb||16||5d||< 1||0||10||1d|
|Lacrimation increased||5||0||4||< 1d||4||0|
|Respiratory, Thoracic, and Mediastinal Disorders|
|Gastroesophageal reflux diseaseb||7||1d||8||0||6||0|
|Skin and Subcutaneous Tissue Disorders|
|Nail disorderb||24||2d||10||< 1d||9||0|
|Palmar-plantar erythrodysesthesia syndromeb,f||64||18d||63||17d||8||2d|
|Skin exfoliationb||5||< 1d||3||0||2||0|
|Musculoskeletal, Connective Tissue, and Bone Disorders|
|General Disorders and Administrative Site Conditions|
|Chest painb||4||1d||< 1||0||5||1d|
|a System organ class presented
as outlined in Guidelines for Preparing Core Clinical Safety Information
on Drugs by the Council for International Organizations of Medical Sciences
b A composite of multiple MedDRA Preferred Terms.
c NCI CTC grading for febrile neutropenia ranges from Grade 3 to 5. Three patients (1%) experienced Grade 5 (fatal) febrile neutropenia. Other neutropenia-related deaths (9) occurred in the absence of reported febrile neutropenia [see WARNINGS AND PRECAUTIONS].
d No grade 4 reports.
e Peripheral sensory neuropathy (graded with the NCI CTC scale) was defined as the occurrence of any of the following: areflexia, burning sensation, dysesthesia, hyperesthesia, hypoesthesia, hyporeflexia, neuralgia, neuritis, neuropathy, neuropathy peripheral, neurotoxicity, painful response to normal stimuli, paresthesia, pallanesthesia, peripheral sensory neuropathy, polyneuropathy, polyneuropathy toxic and sensorimotor disorder. Peripheral motor neuropathy was defined as the occurrence of any of the following: multifocal motor neuropathy, neuromuscular toxicity, peripheral motor neuropathy, and peripheral sensorimotor neuropathy.
f Palmar-plantar erythrodysesthesia (hand-foot syndrome) was graded on a 1-3 severity scale in Study 046.
Table 5: Hematologic Abnormalities in Patients with Metastatic
or Locally Advanced Breast Cancer Treated with IXEMPRA
|IXEMPRA with capecitabine n=369||Capecitabine n=368||IXEMPRA monotherapy n=126|
|Grade 3 (%)||Grade 4 (%)||Grade 3 (%)||Grade 4 (%)||Grade 3 (%)||Grade 4 (%)|
|a G-CSF (granulocyte colony stimulating factor) or GM-CSF (granulocyte macrophage stimulating factor) was used in 20% and 17% of patients who received IXEMPRA in Study 046 and Study 081, respectively.|
The following serious adverse reactions were also reported in 1323 patients treated with IXEMPRA as monotherapy or in combination with other therapies in Phase 2 and 3 studies.
Blood and Lymphatic System Disorders: coagulopathy, lymphopenia
Hepatobiliary Disorders: acute hepatic failure, jaundice
Skin and Subcutaneous Tissue Disorders: erythema multiforme
Musculoskeletal, Connective Tissue Disorders, and Bone Disorders: muscular weakness, muscle spasms, trismus
Renal and Urinary Disorders: nephrolithiasis, renal failure
General Disorders and Administration Site Conditions: chills
Investigations: increased transaminases, increased blood alkaline phosphatase, increased gamma-glutamyltransferase
Radiation recall has been reported during postmarketing use of IXEMPRA. Because this reaction was reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
Read the Ixempra (ixabepilone) Side Effects Center for a complete guide to possible side effects
Effect of Other Drugs on Ixabepilone
Drugs That May Increase Ixabepilone Plasma Concentrations
CYP3A4 Inhibitors: Coadministration of ixabepilone with ketoconazole, a potent CYP3A4 inhibitor, increased ixabepilone AUC by 79% compared to ixabepilone treatment alone. If alternative treatment cannot be administered, a dose adjustment should be considered. The effect of mild or moderate inhibitors (eg, erythromycin, fluconazole, or verapamil) on exposure to ixabepilone has not been studied. Therefore, caution should be used when administering mild or moderate CYP3A4 inhibitors during treatment with IXEMPRA, and alternative therapeutic agents that do not inhibit CYP3A4 should be considered. Patients receiving CYP3A4 inhibitors during treatment with IXEMPRA should be monitored closely for acute toxicities (eg, frequent monitoring of peripheral blood counts between cycles of IXEMPRA) [see DOSAGE AND ADMINISTRATION].
Drugs That May Decrease Ixabepilone Plasma Concentrations
CYP3A4 Inducers: IXEMPRA is a CYP3A4 substrate. Coadministration of IXEMPRA with rifampin, a potent CYP3A4 inducer, decreased ixabepilone AUC by 43% compared to IXEMPRA treatment alone. Other strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifabutin, and phenobarbital) may also decrease ixabepilone concentrations leading to subtherapeutic levels. Therefore, therapeutic agents with low enzyme induction potential should be considered for coadministration with IXEMPRA. St. John's Wort may decrease ixabepilone plasma concentrations unpredictably and should be avoided. If patients must be coadministered a strong CYP3A4 inducer, a gradual dose adjustment may be considered [see DOSAGE AND ADMINISTRATION].
Effect of Ixabepilone on Other Drugs
Ixabepilone does not inhibit CYP enzymes at relevant clinical concentrations and is not expected to alter the plasma concentrations of other drugs [see CLINICAL PHARMACOLOGY].
In patients with cancer who received ixabepilone (40 mg/m²) in combination with capecitabine (1000 mg/m²), ixabepilone Cmax decreased by 19%, capecitabine Cmax decreased by 27%, and 5-fluorouracil AUC increased by 14%, as compared to ixabepilone or capecitabine administered separately. The interaction is not clinically significant given that the combination treatment is supported by efficacy data.
Read the Ixempra Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 12/28/2016
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