Recommended Topic Related To:

Ixempra

"The U.S. Food and Drug Administration today granted accelerated approval to Perjeta (pertuzumab) as part of a complete treatment regimen for patients with early stage breast cancer before surgery (neoadjuvant setting). Perjeta is the first FDA-ap"...

Ixempra

Side Effects
Interactions

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections.

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
  Febrile neutropenia 5 4c 1 1d 3 3d
Immune System Disorders
  Hypersensitivityb 2 1d 0 0 5 1d
Metabolism and Nutrition Disorders
  Anorexiab 34 3d 15 1d 19 2d
  Dehydrationb 5 2 2 < 1d 2 1d
Psychiatric
  Insomniab 9 < 1d 2 0 5 0
Nervous System Disorders
  Peripheral neuropathy            
    Sensory neuropathyb,e 65 21 16 0 62 14
    Motor neuropathyb 16 5d < 1 0 10 1d
  Headache 8 < 1d 3 0 11 0
  Taste disorderb 12 0 4 0 6 0
  Dizziness 8 1d 5 1d 7 0
Eye Disorders
  Lacrimation increased 5 0 4 < 1d 4 0
Vascular Disorders
  Hot flushb 5 0 2 0 6 0
Respiratory, Thoracic, and Mediastinal Disorders
  Dyspneab 7 1 4 1 9 1d
  Coughb 6 0 2 0 2 0
Gastrointestinal Disorders
  Nausea 53 3d 40 2d 42 2d
  Vomitingb 39 4d 24 2 29 1d
  Stomatitis/mucositisb 31 4 20 3d 29 6
  Diarrheab 44 6d 39 9 22 1d
  Constipation 22 0 6 < 1d 16 2d
  Abdominal painb 24 2d 14 1d 13 2d
  Gastroesophageal reflux diseaseb 7 1d 8 0 6 0
Skin and Subcutaneous Tissue Disorders
  Alopeciab 31 0 3 0 48 0
  Skin rashb 17 1d 7 0 9 2d
  Nail disorderb 24 2d 10 < 1d 9 0
  Palmar-plantar erythrodysesthesia syndromeb,f 64 18d 63 17d 8 2d
  Pruritus 5 0 2 0 6 1d
  Skin exfoliationb 5 < 1d 3 0 2 0
  Skin hyperpigmentationb 11 0 14 0 2 0
Musculoskeletal, Connective Tissue, and Bone Disorders
  Myalgia/arthralgiab 39 8d 5 < 1d 49 8d
  Musculoskeletal painb 23 2d 5 0 20 3d
General Disorders and Administrative Site Conditions
  Fatigue/astheniab 60 16 29 4 56 13
  Edemab 8 0 5 < 1d 9 1d
  Pyrexia 10 1d 4 0 8 1d
  Painb 9 1d 2 0 8 3d
  Chest painb 4 1d < 1 0 5 1d
Investigations
  Weight decreased 11 0 3 0 6 0
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 (CIOMS).
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

Hematology Parameter Study046 Study081
IXEMPRA with capecitabine n=369 Capecitabine n=368 IXEMPRA monotherapy n=126
Grade 3 (%) Grade 4 (%) Grade 3 (%) Grade 4 (%) Grade 3 (%) Grade 4 (%)
Neutropeniaa 32 36 9 2 31 23
Leukopenia (WBC) 41 16 5 1 36 13
Anemia (Hgb) 8 2 4 1 6 2
Thrombocytopenia 5 3 2 2 5 2
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.

Infections and Infestations: sepsis, pneumonia, infection, neutropenic infection, urinary tract infection, bacterial infection, enterocolitis, laryngitis, lower respiratory tract infection

Blood and Lymphatic System Disorders: coagulopathy, lymphopenia

Metabolism and Nutrition Disorders: hyponatremia, metabolic acidosis, hypokalemia, hypovolemia

Nervous System Disorders: cognitive disorder, syncope, cerebral hemorrhage, abnormal coordination, lethargy

Cardiac Disorders: myocardial infarction, supraventricular arrhythmia, left ventricular dysfunction, angina pectoris, atrial flutter, cardiomyopathy, myocardial ischemia

Vascular Disorders: hypotension, thrombosis, embolism, hemorrhage, hypovolemic shock, vasculitis

Respiratory, Thoracic, and Mediastinal Disorders: pneumonitis, hypoxia, respiratory failure, acute pulmonary edema, dysphonia, pharyngolaryngeal pain

Gastrointestinal Disorders: ileus, colitis, impaired gastric emptying, esophagitis, dysphagia, gastritis, gastrointestinal hemorrhage

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

Postmarketing Experience

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

DRUG INTERACTIONS

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].

Capecitabine

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: 10/27/2011
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
A A A

Ixempra - User Reviews

Ixempra User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Ixempra sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Breast Cancer

Find support and advances in treatment.