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Herzuma ® is trastuzumab Brought to you by Napp, your experienced partner in biosimilar medicines with proven similarity to reference i.v. trastuzumab in terms of clinical effi cacy, safety and immunogenicity. 1,2 SIMILAR WHERE IT MATTERS References: 1. Stebbing J, et al. Lancet Oncol 2017;18:917–28. 2. Esteva F.J, et al. Cancer Chemother Pharmacol 2018;81:505–514. SWITCH YOUR TRASTUZUMAB BRAND TO HERZUMA AND DISCOVER THE BENEFITS FOR YOUR TRUST Prescribing information Herzuma ® ▼ (trastuzumab) 150mg powder for concentrate for solution for infusion Prescribing Information United Kingdom Please read the Summary of Product Characteristics (SPC) before prescribing. Presentation Type I glass vials, with fl uroTec-coated butyl rubber stopper. Each vial contains 150mg of trastuzumab. Indications Adult patients: HER2 positive metastatic breast cancer (MBC): (i) as monotherapy following at least 2 prior chemotherapy regimens, including an anthracycline and a taxane, unless unsuitable. Hormone receptor positive patients must have failed hormonal therapy, unless unsuitable. (ii) in combination with paclitaxel for patients who have not received chemotherapy and anthracyclines are not suitable. (iii) in combination with docetaxel for patients who have not received chemotherapy. (iv) in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive MBC, not previously treated with trastuzumab. HER2 positive early breast cancer (EBC): (i) following surgery, chemotherapy (neo/adjuvant) and radiotherapy (if applicable). (ii) following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel. (iii) in combination with adjuvant chemotherapy of docetaxel and carboplatin. (iv) for locally advanced (including infl ammatory) disease or tumours > 2cm in diameter, in combination with neoadjuvant chemotherapy followed by adjuvant Herzuma. HER2 positive metastatic gastric cancer (MGC): in combination with capecitabine or 5-fl uorouracil and cisplatin for patients who have not received prior anti-cancer treatment. Dosage and administration HER2 testing is mandatory prior to Herzuma. Check vial labels to ensure trastuzumab not trastuzumab emtansine is prepared. Only physicians experienced with cytotoxic chemotherapy should initiate treatment with Herzuma. Dose (MBC): (i) loading dose 8mg/kg body weight; subsequent doses 6mg/kg repeated at 3-weekly intervals; alternatively (ii) loading dose 4mg/ kg body weight; subsequent doses 2mg/kg weekly. Dose (EBC): (i) loading dose 8mg/kg body weight; subsequent doses 6mg/kg repeated at 3-weekly intervals; alternatively (ii) loading dose 4mg/ kg body weight; subsequent doses 2mg/kg weekly concomitantly with paclitaxel following chemotherapy with doxorubicin and cyclophosphamide. Dose (MGC): loading dose 8mg/kg body weight; subsequent doses 6mg/kg body weight repeated at 3-weekly intervals. Patients with EBC should be treated for 1 year or until disease recurrence. In MBC and MGC, administer until disease progression. Initial loading dose should be administered as a 90-minute IV infusion; if well tolerated, subsequent doses can be administered as a 30-minute IV infusion. Do not administer as an IV push or bolus. Observe for infusion-related symptoms for at least 6 hours following start of fi rst infusion and for 2 hours for subsequent infusions. Interruption of infusion may help control infusion-related symptoms; consider resuming when symptoms abate. Resuscitation equipment must be available. Contraindications Hypersensitivity to trastuzumab, murine proteins or any of the excipients; severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy. Precautions and warnings To improve the traceability of medicinal products, the tradename and batch number of the administered product should be clearly recorded in the patient fi le. Cardiac dysfunction: Increased risk of congestive heart failure (CHF) or asymptomatic cardiac dysfunction observed in patients receiving monotherapy or in combination with paclitaxel or docetaxel, particularly following anthracycline-containing chemotherapy. May be moderate to severe, has been fatal. Caution in patients with increased cardiac risk e.g. symptomatic CHF, history of hypertension or coronary artery disease and in EBC or in those with an LVEF of <55%. Avoid concomitant use of anthracyclines in adjuvant and metastatic settings, only use neoadjuvantly in chemotherapy-naïve EBC patients and only with low-dose anthracycline regimens. There is limited experience of neoadjuvant use, with concurrent anthracyclines in patients >65 years. Avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor cardiac function at baseline every 3 months during treatment and every 6 months, up to 24 months, following discontinuation. Further monitoring recommended if anthracyclines are used; yearly up to 5 years from last administration, or longer if a continuous decrease of LVEF is observed. Consider discontinuing treatment in patients with asymptomatic LVEF decreases, symptomatic CHF or patients who develop clinically signifi cantly heart failure unless benefi ts outweigh risks. Most who developed CHF in clinical trials improved with appropriate treatment and continued trastuzumab therapy without additional clinical cardiac events. Not recommended in EBC patients with history of myocardial infarction, angina pectoris requiring medical treatment, CHF (NHYA Class II-IV), LVEF < 55%, other cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically signifi cant cardiac valvular disease, poorly controlled hypertension and hemodynamic effective pericardial effusion. Date of preparation: March 2018 UK/HER-18020 Infusion related reactions (IRRs): Serious IRRs reported, pre- medication may reduce the risk. Should IRR occur, discontinue or slow the rate of infusion and monitor patient until resolution of all symptoms. Majority of patients experienced resolution and subsequently received further infusions. Serious IRRs have been successfully treated with oxygen, beta-agonists and corticosteroids. Fatal outcomes are rare and have occurred within hours and up to one week following infusion. Pulmonary events: Severe pulmonary events reported, occasionally fatal. May occur as part of IRR or with delayed onset. Risk factors include prior or concomitant therapy with other anti-neoplastic therapies such as taxanes, gemcitabine, vinorelbine and radiation therapy. Patients experiencing dyspnoea at rest may be at increased risk of a fatal IRR and/or pulmonary events and should not be treated with Herzuma. Caution should be exercised for pneumonitis, especially with concomitant taxanes. Interactions No formal medicinal product interaction studies have been performed. Clinically signifi cant interactions between Herzuma and the concomitant medicinal products used in clinical trials have not been observed. Fertility, pregnancy and lactation Women of childbearing potential should be advised to use effective contraception during treatment with Herzuma and for 7 months after last dose. Herzuma should not be administered during pregnancy unless potential benefi t outweighs risk. Oligohydramnios reported in post-marketing, some associated with fatal pulmonary hypoplasia of the foetus. Women should not breast-feed during Herzuma therapy and for 7 months after last dose. Close monitoring of pregnant women receiving Herzuma or within 7 months following the last dose of Herzuma is recommended. Side effects Very common ( ≥1/10) and common ( ≥1/100 to <1/10): infection, nasopharyngitis, neutropenic sepsis, cystitis, herpes zoster, infl uenza, sinusitis, skin infection, rhinitis, upper respiratory tract infection, urinary tract infection, erysipelas, cellulitis, pharyngitis, febrile neutropenia, anaemia, neutropenia, leukopenia, thrombocytopenia, hypersensitivity, weight loss, anorexia, insomnia, anxiety, depression, thinking abnormal, tremor, dizziness, headache, paraesthesia, dysguesia, peripheral neuropathy, hypertonia, somnolence, ataxia, conjunctivitis, lacrimation increased, dry eye, blood pressure decreased, blood pressure increased, heart beat irregular, palpitation, cardiac fl utter, ejection fraction decreased, cardiac failure (congestive), supraventricular tachyarrhythmia, cardiomyopathy, hot fl ush, hypotension, vasodilation, wheezing, dyspnoea, cough, epistaxis, rhinorrhoea, pneumonia, asthma, lung disorder, pleural effusion, diarrhoea, vomiting, nausea, lip swelling, abdominal pain, dyspepsia, constipation, stomatitis, pancreatitis, haemorrhoids, dry mouth, hepatocellular injury, hepatitis, liver tenderness, erythema, rash, swelling face, alopecia, nail disorder, palmar-plantar erythrodysaesthesia syndrome, acne, dry skin, ecchymosis, hyperhidrosis, maculopapular rash, pruritus, onychoclasis, dermatitis, arthralgia, muscle tightness, myalgia, arthritis, back pain, bone pain, muscle spasms, neck pain, pain in extremity, renal disorder, breast infl ammation, asthenia, chest pain, chills, fatigue, infl uenza-like symptoms, infusion related reaction, pain, pyrexia, mucosal infl ammation, peripheral oedema, malaise, oedema, contusion. Uncommon (<1/100) but potentially serious or fatal: sepsis, malignant neoplasm progression, neoplasm progression, anaphylactic reaction, anaphylactic shock, paresis, brain oedema, papilloedema, retinal haemorrhage, deafness, pericardial effusion, cardiogenic shock, pericarditis, bradycardia, pneumonitis, pulmonary fi brosis, respiratory distress, respiratory failure, acute pulmonary oedema, acute respiratory distress syndrome, bronchospasm, hypoxia, oxygen saturation decreased, laryngeal oedema, orthopnoea, pulmonary oedema, interstitial lung disease, hepatic failure, urticaria, angioedema, glomerulonephritis membranous, glomerulonephropathy, renal failure, oligohydramnios, renal hypoplasia, pulmonary hypoplasia. Please refer to the SPC for further information and a full list of side effects. Legal category POM. Presentation and basic NHS costs 1 vial of 150mg: £366.66. Marketing authorisation number EU/1/17/1257/001 Marketing authorisation holder Celltrion Healthcare Hungary Kft 1062 Budapest. Vácí út 1-3. 4. WestEnd Offi ce Building B torony. Hungary. For medical information enquiries, please contact [email protected]. ® HERZUMA is a registered trade mark of Celltrion, Inc. and is used under licence © 2018 Napp Pharmaceuticals Limited Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to NappxPharmaceuticals Limited on 01223 424444. PI Code UK/HER-18003 Date of preparation February 2018