Ixabepilone

Ixabepilone is used to treat advanced breast cancer.

Ixabepilone is usually given after other cancer medications have been tried without successful treatment.

Ixabepilone may also be used for purposes not listed in this medication guide.

Do not use ixabepilone if you are pregnant. It could harm the unborn baby.

You should not receive this medication if you are allergic to ixabepilone, or to a medication ingredient called Cremophor (synthetic castor oil). You may not be able to receive ixabepilone if you have severe liver disease, or severely low platelets or white blood cell counts.

Before you receive ixabepilone, tell your doctor if you have liver disease, heart disease, nerve problems, diabetes, bone marrow suppression, or a weak immune system.

Ixabepilone can lower blood cells that help your body fight infections. Avoid being near people who are sick or have infections. Your blood may need to be tested often. Visit your doctor regularly.

Tell your doctor at once if you develop signs of infection, such as fever, chills, body aches, flu symptoms, pale skin, easy bruising or bleeding, or sores in your mouth and throat.

Avoid drinking alcohol during your treatment with ixabepilone.

You should not receive this medication if you are allergic to ixabepilone, or to a medication ingredient called Cremophor (synthetic castor oil). You may not be able to receive ixabepilone if you have severe liver disease, or severely low platelets or white blood cell counts.

To make sure you can safely receive ixabepilone, tell your doctor if you have any of these other conditions:

• liver disease;
• heart disease;
• nerve problems (especially in your hands or feet);
• diabetes; or
• bone marrow suppression or weak immune system.

Do not use ixabepilone if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

It is not known whether ixabepilone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while receiving ixabepilone.

IXEMPRA (ixabepilone) is a microtubule inhibitor belonging to a class of antineoplastic agents, the epothilones and their analogs. The epothilones are isolated from the myxobacterium Sorangium cellulosum. Ixabepilone is a semisynthetic analog of epothilone B, a 16-membered polyketide macrolide, with a chemically modified lactam substitution for the naturally existing lactone.

The chemical name for ixabepilone is (1S,3S,7S,10R,11S,12S,16R)-7,11dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]17-oxa-4-azabicyclo[14.1.0] heptadecane-5,9-dione, and it has a molecular weight of 506.7. Ixabepilone has the following structural formula:

IXEMPRA (ixabepilone) for injection is intended for intravenous infusion only after constitution with the supplied DILUENT and after further dilution with a specified infusion fluid [see Instructions for Preparation and IV Administration]. IXEMPRA (ixabepilone) for injection is supplied as a sterile, non-pyrogenic, single-use vial providing 15 mg or 45 mg ixabepilone as a lyophilized white powder. The DILUENT for IXEMPRA is a sterile, non-pyrogenic solution of 52.8% (w/v) purified polyoxyethylated castor oil and 39.8% (w/v) dehydrated alcohol, USP. The IXEMPRA (ixabepilone) for injection and the DILUENT for IXEMPRA are co-packaged and supplied as IXEMPRA Kit.

Experience with overdose of IXEMPRA is limited to isolated cases. The adverse reactions reported in these cases included peripheral neuropathy, fatigue, musculoskeletal pain/myalgia, and gastrointestinal symptoms (nausea, anorexia, diarrhea, abdominal pain, stomatitis). The highest dose mistakenly received was 100 mg/m² (total dose 185 mg).

There is no known antidote for overdosage of IXEMPRA. In case of overdosage, the patient should be closely monitored and supportive treatment should be administered.

Management of overdose should include supportive medical interventions to treat the presenting clinical manifestations.

• Breast Cancer
• Chemotherapy Treatment for Breast Cancer

Storage

Parenteral

2–8° C in original package; protect from light.1

Reconstituted solutions may be stored at room temperature for ≤1 hour in room light.1

Solutions diluted in appropriate injections are stable at room temperature and room light for ≤6 hours.1 2 (See Dilution under Dosage and Administration.)

• A microtubule inhibitor; binds to β-tubulin subunits on microtubules; stabilizes and suppresses microtubule activity resulting in mitotic arrest and apoptosis.1 13 15 17 18 19

• Active in xenografts resistant to multiple antineoplastic agents, including taxanes, anthracyclines, and vinca alkaloids.1 13 19

• Synergistic antitumor activity demonstrated in combination with capecitabine in vivo.1

• Has antiangiogenic activity.1

• Importance of reading patient information provided by the manufacturer.1 21

• Risk of neuropathy.1 2 Importance of patients notifying clinicians if they develop any numbness, tingling, or burning of the hands or feet.1 2 21

• Importance of patients notifying clinicians if they develop a fever of ≥100.5°F or other signs and symptoms of potential infection (e.g., chills, cough, burning or pain upon urination).1 2 21

• Importance of patients notifying clinicians if they experience urticaria, pruritus, rash, flushing, swelling, dyspnea, chest tightness, and/or other hypersensitivity-related symptoms following IV infusion of ixabepilone.1 21

• Importance of patients notifying clinicians if they notice chest pain, difficulty breathing, palpitations, or unusual weight gain.1 21

• Importance of patients informing clinicians if they are allergic to a drug such as paclitaxel that contains polyoxyl 35 castor oil (Cremophor EL, polyethoxylated castor oil).1 2 21

• Importance of patients informing clinicians if they have hepatic impairment.21 Importance of undergoing blood tests to determine liver function before and during ixabepilone therapy.21 Importance of not taking ixabepilone in combination with capecitabine if hepatic impairment is present.21

• Importance of not drinking grapefruit juice while receiving ixabepilone therapy.1 2 21

• Importance of informing patients that Ixempra contains alcohol and may cause drowsiness or dizziness.1 21 Importance of avoiding certain activities (e.g., operating machinery, driving a motor vehicle) if patient feels drowsy or dizzy.1 21

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements (e.g., St. John’s wort), as well as any concomitant illnesses (e.g., diabetes mellitus, liver disease).1 2

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to the fetus.1 21

• Importance of informing patients of other important precautionary information.1 21 (See Cautions.)

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Ixempra Kit: 15 mg (1 ea); 45 mg (1 ea) [contains alcohol, usp, cremophor el]

• Ixempra Kit

• Antineoplastic Agent, Antimicrotubular
• Antineoplastic Agent, Epothilone B Analog

IV: Infuse over 3 hours. Use non-DEHP administration set (eg, polyethylene); filter with a 0.2 to 1.2 micron inline filter. Administration should be completed within 6 hours of preparation. If the dose is increased (above 40 mg/m2) due to concomitant CYP3A4 inducer use, infuse over 4 hours.

Applies to ixabepilone: intravenous powder for solution

Along with its needed effects, ixabepilone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking ixabepilone:

• Black, tarry stools
• body aches or pain
• burning, numbness, tingling, or painful sensations
• burning pain on urination
• chest pain
• chills
• cough
• difficult or labored breathing
• ear congestion
• fever
• headache
• loss of voice
• lower back or side pain
• nasal congestion
• painful or difficult urination
• pale skin
• red, swelling, or painful skin
• runny nose
• scaling of the skin on the hands and feet
• shortness of breath
• sneezing
• sore throat
• sores, ulcers, or white spots on the lips, tongue, or inside the mouth
• swelling of the hands, ankles, feet, or lower legs
• swollen glands
• tightness in the chest
• tingling of the hands and feet
• troubled breathing with exertion
• ulceration of the skin
• unsteadiness or awkwardness
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain
• weakness in the arms, hands, legs, or feet
• wheezing

• Bleeding gums
• blood in the urine or stools
• confusion
• decreased urination
• dizziness
• dry mouth
• fainting
• fast heartbeat
• hives
• hoarseness
• increase in heart rate
• irritation
• itching
• joint pain, stiffness, or swelling
• lightheadedness
• pinpoint red spots on the skin
• rapid breathing
• rash
• sunken eyes
• swelling of the eyelids, face, or lips
• thirst
• trouble with swallowing
• wrinkled skin

Some side effects of ixabepilone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bad, unusual, or unpleasant (after) taste
• bone pain
• change in taste
• cracked lips
• diarrhea
• difficulty having a bowel movement (stool)
• discoloration of the fingernails or toenails
• feeling of warmth
• hair loss or thinning of the hair
• heartburn
• lack or loss of strength
• loss of appetite
• nausea
• redness of the face, neck, arms, and occasionally, upper chest
• stomach pain
• sudden sweating
• swelling or inflammation of the mouth
• vomiting
• weight loss

• Darkening of the skin
• flaking and falling off of the skin
• sleeplessness
• trouble with sleeping
• unable to sleep
• watering of the eyes

40 mg/m2 infused intravenously over 3 hours every 3 weeks. The dosage for patients with a BSA exceeding 2.2 m2 should be calculated based on a 2.2 m2 body surface area.

Premedication: all patients must be premedicated approximately 1 hour prior to ixabepilone administration (to minimize the chance of a hypersensitivity reaction) as follows:
1. with an H1 antagonist (e.g., diphenhydramine 50 mg orally or an equivalent agent) plus
2. an H2 antagonist (e.g., ranitidine 150 mg to 300 mg orally or an equivalent agent)

Patients experiencing a hypersensitivity reaction in one cycle of ixabepilone treatment must be premedicated in subsequent cycles with a corticosteroid (e.g., dexamethasone 20 mg intravenously 30 minutes prior to ixabepilone infusion, or orally 60 minutes prior to infusion) in addition to the H1 and H2 antagonists. Extension of the infusion time should also be considered.