Intravenous Locally advanced breast cancer, Metastatic breast cancer
Adult: As monotherapy in patients whose tumours are resistant or refractory to anthracyclines, taxanes, and capecitabine; or in combination with capecitabine in patients whose tumours are resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane-resistant and for whom further anthracycline therapy is contraindicated: 40 mg/m2 via infusion over 3 hours once every 3 weeks. Max: 88 mg. Continue until disease progression or unacceptable toxicity. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guidelines).
Special Patient Group
Patients taking strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole): Avoid concomitant use. If use cannot be avoided, reduce ixabepilone dose to 20 mg/m2. If the strong inhibitor is discontinued, resume the previous ixabepilone dose (at 1 week after discontinuing the inhibitor) to what was used before initiating the strong inhibitor.
Patients taking strong CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampicin, phenobarbital): Avoid concomitant use. If use cannot be avoided, gradually increase ixabepilone dose from 40 mg/m2 to 60 mg/m2 as tolerated. Administer ixabepilone as a 4-hour infusion and monitor patients carefully for adverse reactions.
Hepatic Impairment
As monotherapy: AST and ALT >2.5 to ≤10 times upper limit of normal (ULN) and bilirubin >1 to ≤1.5 times ULN: 32 mg/m2; AST and ALT ≤10 times ULN and bilirubin >1.5 to ≤3 times ULN: 20-30 mg/m2; AST or ALT >10 times ULN or bilirubin >3 times ULN: Not recommended. Further decreases in subsequent courses should be based on individual tolerance. In combination with capecitabine: AST or ALT >2.5 times ULN or bilirubin >1 times ULN: Contraindicated.
Reconstitution
Reconstitute with the provided diluent and further dilute to a concentration of 0.2-0.6 mg/mL prior to administration (refer to specific product guideline).
Contraindications
History of severe hypersensitivity to polyoxyethylated castor oil (Cremophor EL) or its derivatives, neutrophil count <1,500/mm3 or platelet count <100,000/mm3. AST or ALT >2.5 times ULN or bilirubin >1 times ULN (ixabepilone and capecitabine combination therapy). Pregnancy and lactation.
Special Precautions
Patient with a history of cardiac disease; diabetes, pre-existing peripheral neuropathy. Patients taking strong CYP3A4 inhibitors or inducers. Premedicate with an H1-antagonist (oral diphenhydramine 50 mg or equivalent) and an H2-antagonist approx 1 hour prior to infusion; for patients with a history of ixabepilone hypersensitivity, administer corticosteroids (e.g. dexamethasone 20 mg orally 1 hour before or IV 30 minutes before infusion) in addition to H1 and H2-antagonist. Hepatic impairment.
Adverse Reactions
Significant: Peripheral neuropathy (motor and sensory), myocardial ischaemia, ventricular dysfunction, supraventricular arrhythmias. Blood and lymphatic system disorders: Leucopenia, anaemia, thrombocytopenia. Cardiac disorders: Chest pain. Eye disorders: Increased lacrimation. Gastrointestinal disorders: Nausea, vomiting, stomatitis, mucositis, diarrhoea, constipation, abdominal pain, taste disorder, GERD. General disorders and administration site conditions: Fatigue, asthenia, oedema, pyrexia. Investigations: Decreased weight. Metabolism and nutrition disorders: Anorexia, dehydration. Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, musculoskeletal pain. Nervous system disorders: Headache, dizziness. Psychiatric disorders: Insomnia. Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection, cough, dyspnoea. Skin and subcutaneous tissue disorders: Alopecia, palmar-plantar erythrodysaesthesia syndrome, nail disorder, pruritus, rash, skin exfoliation or hyperpigmentation. Vascular disorders: Hot flush. Potentially Fatal: Myelosuppression, particularly neutropenia (including, febrile neutropenia, and infections); severe hypersensitivity reactions, including anaphylaxis.
This drug may cause dizziness or drowsiness, if affected, do not drive or operate machinery.
Monitoring Parameters
Verify pregnancy status in women of childbearing potential before initiating treatment. Monitor CBC with differential at baseline and frequently during treatment, hepatic function (ALT, AST, bilirubin) at baseline and periodically. Assess for signs or symptoms of hypersensitivity reactions, neuropathy and cardiac ischaemia or impaired cardiac function.
Increased plasma concentration with grapefruit juice and other grapefruit products; avoid concomitant administration. St. John's wort may decrease the plasma concentration of ixabepilone.
Action
Description: Mechanism of Action: Ixabepilone is a semi-synthetic epothilone B analogue that binds directly to the β-tubulin subunits on microtubules, stabilising microtubule activity, thus arresting the cell cycle and inducing apoptosis. Pharmacokinetics: Absorption: Time to peak plasma concentration: 3 hours. Distribution: Extensively distributed. Plasma protein binding: 67-77%. Metabolism: Extensively metabolised in the liver mainly via oxidation by CYP3A4 isoenzyme. Excretion: Via faeces (65%, mainly as metabolites and approx 1.6% as unchanged drug); urine (21%, mainly as metabolites and approx 5.6% as unchanged drug). Elimination half-life: Approx 52 hours.
Chemical Structure
Ixabepilone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6445540, Ixabepilone. https://pubchem.ncbi.nlm.nih.gov/compound/6445540. Accessed Aug. 25, 2022.
Storage
Store between 2-8°C. Protect from light. Reconstituted solution (in vial): May store for up to 1 hour at room temperature and room light. Diluted infusion solution (diluted in appropriate solution for infusion): Stable for 6 hours at room temperature and room light (infusion must be completed within 6 hours). This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01DC04 - ixabepilone ; Belongs to the class of other cytotoxic antibiotics. Used in the treatment of cancer.
References
Anon. Ixabepilone. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/08/2022.Anon. Ixabepilone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/08/2022.Buckingham R (ed). Ixabepilone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/08/2022.Ixempra (R-Pharm US Operating, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/08/2022.Ixempra Kit for Injection, for Intravenous Infusion (Baxter Oncology GmbH). U.S. FDA. https://www.fda.gov. Accessed 08/08/2022.
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