May 2019

Important New Products

• Inotuzumab ozogamicin (rch) (Besponsa) is a CD22-targeted antibody-drug conjugate (ADC). It is a humanised IgG4 antibody which specifically recognises human CD22. The small molecule, N‑acetyl-gamma-calicheamicin, is a cytotoxic agent that is covalently attached to the antibody via an acid-cleavable linker. Nonclinical data suggest that the anticancer activity of inotuzumab ozogamicin is due to the binding of the ADC to CD22-expressing tumour cells, followed by internalisation of the ADC-CD22 complex, and the intracellular release of N‑acetyl‑gamma‑calicheamicin dimethylhydrazide via hydrolytic cleavage of the linker. Activation of N-acetyl-gamma-calicheamicin dimethylhydrazide induces double-strand DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death. Besponsa is indicated for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL). Use of Besponsa should be initiated and supervised by a physician experienced in the treatment of haematological malignancies. Besponsa is contraindicated in patients who have experienced prior confirmed severe or ongoing veno-occlusive liver disease/sinusoidal obstruction syndrome (VOD/SOS) and patients with serious ongoing hepatic disease (e.g. cirrhosis, nodular regenerative hyperplasia, active hepatitis). Besponsa powder for injection vial contains inotuzumab ozogamicin (rch) 1 mg in a pack size of 1.
   
• Neratinib (maleate) (Nerlynx) is an irreversible inhibitor of 3 epidermal growth factor receptors (EGFRs): EGFR (encoded by ERBB1), HER2 (encoded by ERBB2), and HER4 (encoded by ERBB4). Neratinib binds to the HER2 receptor, reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signalling pathways, and inhibits tumour cell proliferation in vitro. In vivo, oral administration of neratinib inhibited tumour growth in mouse xenograft models with tumour cell lines expressing HER2 and EGFR. Nerlynx is indicated for the extended adjuvant treatment of adults with early-stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab based therapy. Nerlynx should be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products. Nerlynx is contraindicated in severe hepatic impairment and with concomitant strong CYP3A4/P-gp inducers (carbamazepine, phenobarbital, phenytoin, St John’s wort, rifampicin) and moderate CYP3A4/P-gp inhibitors (fluconazole, diltiazem, verapamil, erythromycin). Nerlynx tablets contain neratinib (maleate) 40 mg and are available in a pack size of 180.
   
• Rurioctocog alfa pegol (rch) (Adynovate) is a full-length recombinant human coagulation factor VIII with an extended half-life. Its therapeutic activity is derived from its parent molecule, octocog alfa, covalently conjugated with the PEG reagent, which targets lysine residues. The PEG moiety is conjugated to the octocog alfa molecule to increase the plasma half-life through the reduction of the low density lipoprotein receptor-related protein-1 (LRP-1) receptor-mediated clearance of the factor VIII molecule. Adynovate is a long-acting antihaemophilic factor (recombinant) indicated in haemophilia A (congenital factor VIII deficiency) patients for: control and prevention of bleeding episodes, routine prophylaxis to prevent or reduce the frequency of bleeding episodes, perioperative management (surgical prophylaxis). Adynovate is not indicated for the treatment of von Willebrand disease. Treatment with Adynovate should be under the supervision of a physician experienced in the treatment of haemophilia. Adynovate is contraindicated in known life-threatening hypersensitivity reaction, including anaphylaxis, to octocog alfa, or mouse or hamster protein. Adynovate powder for injection vial contains rurioctocog alfa pegol (rch) 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU or 3000 IU with 2 mL or 5 mL solvent (vial) in a pack of 1.
   
• Tezacaftor/ivacaftor (Symdeko) contains two components: tezacaftor, a broad-acting cystic fibrosis transmembrane conductance regulator (CFTR) corrector that facilitates the cellular processing and trafficking of normal or multiple mutant forms of CFTR (including F508del-CFTR), and ivacaftor, which potentiates the channel-open probability (or gating) of CFTR at the cell. The combined effect is increased quantity and function of CFTR at the cell surface, resulting in increases in chloride transport, airway surface liquid height, and ciliary beat frequency. Symdeko is indicated for the treatment of patients ≥ 12 years with cystic fibrosis who are homozygous for the F508del mutation or who have at least one mutation in the CFTR gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence. Symdeko should only be prescribed by physicians with experience in the treatment of cystic fibrosis. Symdeko tablets are available in a composite pack of 56 (28 tablets of tezacaftor 100 mg/ivacaftor 150 mg and 28 tablets of ivacaftor 150 mg).

New Indications

• Eltrombopag (Revolade) in combination with standard immunosuppressive therapy is now indicated for the first-line treatment of adult and paediatric patients ≥ 2 years with severe aplastic anaemia.
   
• Interferon beta-1a (rch) (Avonex) is now indicated for the treatment of secondary progressive multiple sclerosis (MS) in patients in whom relapse is still a feature. Avonex should not be initiated in patients who have not experienced a relapse in the previous 12 months.
   
• Pembrolizumab (rch) (Keytruda) in combination with carboplatin and either paclitaxel or nab‑paclitaxel is now indicated for the first-line treatment of patients with metastatic squamous non‑small cell lung carcinoma.
   
• Tocilizumab (rch) (Actemra) is now indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) in adults and paediatric patients ≥ 2 years (IV formulation only).

New Contraindications

• Abiraterone acetate (Zytiga) plus prednisone/prednisolone is now contraindicated in combination with radium 223 dichloride.
   
• Atorvastatin (calcium) (Lipitor) is now contraindicated with concomitant glecaprevir/pibrentasvir.
   
• Budesonide (Rhinocort) is now contraindicated in patients with hypersensitivity to other corticosteroids.
   
• Darunavir (Prezista) is now contraindicated with concomitant dapoxetine, ivabradine, lomitapide or naloxegol.
   
• Netupitant/palonosetron (HCl) (Akynzeo) is now contraindicated during pregnancy.
   
• Sodium valproate (Epilim/Epilim IV) is now contraindicated in women of childbearing potential, unless the physician has provided information regarding the potential effects of valproate during pregnancy and recommendations on its use.

This list is a summary of only some of the changes that have occurred over the last month. Before prescribing, always refer to the full product information.

Active Ingredient Naming Changes

In this release, MIMS Australia will be including the following INNs (International Non-proprietary Names) as well as Australian Approved Names (AANs) as part of our push to support the Therapeutic Goods Administration (TGA) active ingredient name changes project.  

MIMS will begin referring to these ingredients by their new names, however, users may continue to search by the old AANs if preferred. ...(more)