Company: Roche Products (Ireland) Ltd.
Legal category: Prescription. Sport permitted.
Active ingredient: Trastuzumab emtansine 100mg, 160mg.
Description: Powder concentrate for solution for infusion.
Presentation: Price available on application.
Indication: As a single agent, for treatment of HER2-positive, unresectable locally advanced or metastatic breast cancer, previously treated with trastuzumab and a taxane, separately or in combination. Patients should have either received prior therapy for locally advanced or metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy.
Pharmacology: Trastuzumab emtansine is a HER2-targeted antibody-drug conjugate which contains the humanised anti-HER2 IgG1, trastuzumab, covalently linked to the microtubule inhibitor DM1 via the stable thioether linker MCC. Emtansine refers to the MCC-DM1 complex. Conjugation of DM1 to trastuzumab confers selectivity of the cytotoxic agent for HER2-overexpressing tumour cells, thereby increasing intracellular delivery of DM1 directly to malignant cells. Upon binding to HER2, trastuzumab emtansine undergoes receptor-mediated internalisation and subsequent lysosomal degradation, resulting in release of DM1-containing cytotoxic catabolites.
Dosage: Adult: 3.6mg/kg bodyweight by intravenous infusion every 3 weeks. Administer first dose as 90 minute infusion. If well tolerated, can administer subsequent doses as 30 minute infusions. Observe patients closely during and for at least 90 minutes after first infusion, and during and for at least 30 minutes after subsequent infusions, for infusion-related reactions (IRRs); slow or interrupt infusion rate if reactions develop. See SPC for dose reduction schedule and for dose modifications for the following adverse reactions: Increased transaminases, hyperbilirubinemia, thrombocytopenia, left ventricular dysfunction. Do not re-escalate dose after it has been reduced. Duration: Continue until disease progression or unacceptable toxicity. Elderly: ≥75 years, limited data. Children: Under 18 years, no relevant use.
Contraindications: Hypersensitivity to the active substance or to any of the excipients. Pregnancy, lactation. Patients should use effective contraception (including male patients or their female partners) and women should not breast feed during therapy and for 7 months following last dose.
Special precautions: Do not administer as an intravenous push or bolus. Life-threatening infusion reactions (permanently discontinue). Suspend if Grade 3 or 4 peripheral neuropathy occurs until resolution to ≤Grade 2. Severe renal impairment (monitor carefully). Interstitial lung disease including pneumonitis (discontinue permanently; patients with dyspnoea at rest due to complications of advanced malignancy and co-morbidities may be at increased risk). Monitor liver function prior to initiation and each dose. Hepatotoxicity (asymptomatic increases in serum transaminases) and serious hepatobiliary disorders, including nodular regenerative hyperplasia (NRH) of the liver, observed. Discontinue permanently if NRH, or serum transaminases >3xULN and concomitant total bilirubin >2x ULN, occur. Test cardiac function prior to initiation and at regular intervals (e.g. every three months) during treatment. Left ventricular ejection fraction (LVEF) <40% observed. Risk factors for a cardiac event include advancing age (>50 years), low baseline LVEF values (<55%), low LVEF levels prior to or following use of paclitaxel in adjuvant setting, prior or concomitant use of antihypertensives, previous therapy with an anthracycline and high BMI (>25kg/m2). Not recommended: Use in patients who had trastuzumab permanently discontinued due to IRRs or hypersensitivity. Thrombocytopenia, and cases of bleeding events with a fatal outcome, observed. Monitor platelet counts prior to each dose. Monitor patients with thrombocytopenia (≤100,000/mm3) and patients on anti-coagulants closely. If platelet count decreases to Grade 3 or greater (<50,000/mm3), do not administer until platelet counts recover to Grade 1 (≥75,000/mm3). Driving/using machines (IRRs).
Drug interactions: Avoid: Strong CYP3A4 inhibitors.
Adverse drug reactions: Urinary tract infection, thrombocytopenia, anaemia, neutropenia, leucopoenia, hypokalaemia, insomnia, peripheral neuropathy, peripheral oedema, headache, dizziness, dysgeusia, memory impairment, haemorrhage, hypertension, epistaxis, cough, dyspnoea, GI upset, rash, pruritus, alopecia, nail disorder, Palmar-plantar erythrodysaesthesia syndrome, urticaria, musculoskeletal pain, arthralgia, myalgia, fatigue, pyrexia, chills, increased transaminases, increased blood alkaline phosphatase, drug hypersensitivity, dry eye, conjunctivitis, blurred vision, increased lacrimation, left ventricular dysfunction, IRRs.
Full prescribing information and references available from Roche Products (Ireland) Ltd. Telephone: (01) 4690700.