Company: Roche Products (Ireland) Ltd.
Legal category: Prescription. Hospital. Sport permitted.
Active ingredient: Pertuzumab 420mg per vial.
Description: Concentrate for solution for infusion.
Presentation: Price available on request.
Indications: For use in combination with trastuzumab and docetaxel in adults with HER2-positive metastatic or locally recurrent unresectable breast cancer, who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease.
Pharmacology: Pertuzumab is a recombinant humanised monoclonal antibody that specifically targets the extracellular dimerisation domain of the human epidermal growth factor receptor 2 protein (HER2), and thereby, blocks ligand-dependent heterodimerisation of HER2 with other HER family members, including EGFR, HER3 and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signalling through two major signal pathways, mitogen-activated protein kinase and phosphoinositide 3-kinase. Inhibition of these signalling pathways can result in cell growth arrest and apoptosis, respectively. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity.
Dosage: Adult: Administer drugs sequentially. Pertuzumab and trastuzumab can be given in any order. When receiving docetaxel, administer after pertuzumab and trastuzumab. Pertuzumab, initial loading dose of 840mg as a 60 minute intravenous infusion, followed every 3 weeks thereafter by maintenance dose of 420mg as a 30 to 60 minute infusion. Trastuzumab, initial loading dose of 8mg/kg body weight as an intravenous infusion followed every 3 weeks thereafter by maintenance dose of 6mg/kg body weight. Docetaxel, initial dose of 75mg/m2, administered thereafter on a 3 weekly schedule; may be escalated to 100mg/m2 on subsequent cycles if initial dose well tolerated. Observe patients for 30 to 60 minutes after each pertuzumab infusion and before start of any subsequent infusion of trastuzumab or docetaxel. Slow or interrupt infusion rate if infusion reactions develop. Dose reductions not recommended for pertuzumab or trastuzumab. If trastuzumab discontinued, discontinue pertuzumab also. If docetaxel discontinued, treatment with pertuzumab and trastuzumab may continue until disease progression or unmanageable toxicity. Elderly: Over 65 years, limited data. Children: Under 18 years, safety and efficacy not established.
Contraindications: Hypersensitivity to the active ingredient or to any of the excipients. Pregnancy, lactation.
Special precautions: Assess left ventricular ejection fraction (LVEF) prior to initiation and every 3 cycles during treatment to ensure LVEF within normal limits. Withhold pertuzumab and trastuzumab for at least 3 weeks for any of the following: Signs suggestive of congestive heart failure (discontinue pertuzumab if symptomatic heart failure confirmed), or a drop in LVEF to <40%, or a LVEF of 40%-45% associated with a fall of ≥10% points below pre-treatment values. If after approximately 3 weeks, LVEF not improved, or declined further, consider discontinuation of pertuzumab and trastuzumab (unless benefits outweigh risks). Discontinue immediately if a NCI-CTCAE Grade 4 reaction (anaphylaxis), bronchospasm or acute respiratory distress syndrome occur. Combination treatment with pertuzumab, trastuzumab and docetaxel increases risk of febrile neutropenia. Use contraception during therapy and for 6 months following last dose. Driving/using machines (if infusion reactions occur).
Drug interactions: None known.
Adverse drug reactions: Upper respiratory tract infection, nasopharyngitis, febrile neutropenia, neutropenia, leucopenia, anaemia, hypersensitivity/ anaphylactic reaction, infusion-related reaction/ cytokine release syndrome, decreased appetite, insomnia, peripheral neuropathy, peripheral sensory neuropathy, headache, dizziness, dysgeusia, increased lacrimation, dyspnoea, cough, GI upset, alopecia, rash, nail disorder, pruritus, dry skin, myalgia, arthralgia, mucositis/ mucosal inflammation, pain, oedema, pyrexia, fatigue, paronychia, left ventricular dysfunction (including congestive heart failure), pleural effusion, chills.
Full prescribing information and references available from Roche Products (Ireland) Ltd. Telephone: (01) 4690700.