June 2023

New Products

• Deucravacitinib (Sotyktu) is a small molecule that selectively inhibits the tyrosine kinase 2 (TYK2) enzyme. It binds to the regulatory domain of TYK2, stabilising an inhibitory interaction between the regulatory and the catalytic domains of the enzyme. This results in allosteric inhibition of receptor-mediated activation of TYK2 and its downstream functions in cells. TYK2 is a member of the Janus kinase (JAK) family. JAK kinases, including TYK2, function in pairs to mediate JAK‑STAT pathways. TYK2 pairs with JAK1 to mediate multiple cytokine pathways and also pairs with JAK2 to transmit signals. The pairing of TYK2 with either JAK1 or JAK2 mediates signalling of a narrower range of cytokines compared with the pairings of JAKs 1/2/3 with each other. The allosteric mechanism of action of deucravacitinib has been shown to inhibit TYK2 with minimal or no inhibition of JAK 1/2/3. TYK2 mediates signalling of interleukin‑23 (IL‑23) cytokine, interleukin‑12 (IL‑12) cytokine, and type I interferons (IFN), which are naturally occurring cytokines involved in inflammatory and immune responses. Deucravacitinib inhibits signalling from IL‑23, IL‑12 and type I IFN and the downstream release of proinflammatory cytokines and chemokines. Sotyktu is indicated for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Sotyktu tablets contain deucravacitinib 6 mg and are available in packs of 28. 
   
• Dostarlimab (Jemperli) is an anti-programmed cell death protein‑1 (PD‑1) IgG4 humanised mAb derived from a stable Chinese hamster ovary cell line. Binding of the PD‑1 ligands, PD‑L1 and PD‑L2, to the PD‑1 receptor found on T cells inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumours and signalling through this pathway can contribute to inhibition of active T cell immune surveillance of tumours. Dostarlimab binds to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2, releasing inhibition of PD-1 pathway‑mediated immune response, including the anti‑tumour immune response. In syngeneic mouse tumour models, blocking PD-1 activity resulted in decreased tumour growth.  Jemperli is indicated with provisional approval as monotherapy for the treatment of adult patients with recurrent or advanced mismatch repair deficient endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen. Jemperli concentrate for infusion contains dostarlimab 500 mg per 10 mL and is available in a pack of 1 vial.
   
• Ivosidenib (Tibsovo) is a small molecule inhibitor of R132‑mutated isocitrate dehydrogenase 1 (IDH1) enzymes. Through a gain of neomorphic function, the mutant IDH1 converts alpha‑ketoglutarate (α‑KG) to 2‑hydroxyglutarate (2‑HG). As 2-HG competitively inhibits α‑KG‑dependent enzymes, including histone and DNA demethylases, its accumulation leads to widespread epigenetic dysregulation. Tibsovo is indicated for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation after at least one prior line of systemic therapy. Tibsovo tablets contain ivosidenib 250 mg and are available in bottles of 60 tablets.
   
• Nivolumab and relatlimab (Opdualag) is a combination of two human IgG4 monoclonal antibodies. Relatlimab binds to the LAG-3 T cell receptor, blocks interaction with its ligands (including major histocompatibility complex Class II) and reduces LAG-3 pathway-mediated inhibition of the immune response. Antagonism of this pathway promotes T cell proliferation and cytokine secretion. Binding of the PD-1 receptor found on T cells to its ligands (PD‑L1 and PD‑L2) inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumours and signalling through this pathway can contribute to inhibition of active T cell immune surveillance of tumours. Nivolumab binds to the PD-1 receptor, blocks interaction with PD-L1 and PD-L2 and reduces PD-1 pathway-mediated inhibition of the immune response, including the anti‑tumour immune response. Combined inhibition of PD-1 (with nivolumab) and LAG-3 (with relatlimab) results in increased T cell activation compared to the effect of either antibody alone. In murine syngeneic tumour models, LAG-3 blockade potentiates the anti-tumour activity of PD‑1 blockade, inhibiting tumour growth and promoting tumour regression. Opdualag is indicated for the treatment of patients with unresectable or metastatic melanoma who are at least 12 years old. Opdualag concentrate for infusion contains nivolumab 240 mg and relatlimab 80 mg per 20 mL and is available in a pack of 1 vial.

New Presentation

• Immunoglobulin, normal (human) (Hizentra AU) is manufactured from human plasma collected in Australia by Australian Red Cross Lifeblood. (Hizentra is manufactured from human plasma collected outside Australia by CSL Plasma.) It is available as a 20% solution for injection in 1 g/5 mL or 4 g/20 mL single vial packs.

New Indications

• Durvalumab (Imfinzi) is now indicated in combination with gemcitabine and cisplatin for the treatment of patients with locally advanced or metastatic biliary tract cancer.
   
• Human papillomavirus 9-valent recombinant vaccine (Gardasil 9) is now indicated in males aged 9-45 years.
   
• Ibrutinib (Imbruvica) is now indicated in combination with venetoclax for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia/small lymphocytic lymphoma.
   
• Obinutuzumab (Gazyva) is now indicated as a pre-treatment to reduce the risk of cytokine release syndrome induced by glofitamab.

New Contraindications

• Dexamethasone phosphate (DBL Dexamethasone Sodium Phosphate Injection) is now contraindicated in bacteraemia, unstable joints, and infection at the injection site e.g., septic arthritis resulting from gonorrhoea or tuberculosis.
   
• Combined oral contraceptives containing ethinylestradiol or ethinylestradiol (betadex clathrate) AND cyproterone acetate, dienogest, drospirenone or levonorgestrel (Diane‑35 ED, Valette, Yaz, Microgynon 20/ 30/ 50 ED, Triquilar ED) are now contraindicated for concomitant use with glecaprevir, pibrentasvir, sofosbuvir, velpatasvir or voxilaprevir, and combinations of these.
   
• Multivitamin for intravenous injection (Cernevit) is now contraindicated in patients with known peanut protein hypersensitivity.
   
• Topiramate (Topamax) is now contraindicated as migraine prophylaxis in pregnancy and in women of childbearing potential if not using a highly effective method of contraception.

Safety Related Changes

• Baricitinib (Olumiant), tofacitinib (Xeljanz) and upadacitinib (Rinvoq). A large post-marketing rheumatoid arthritis safety study of the JAK inhibitor tofacitinib (Oral Surveillance Study) found an increased risk of major cardiovascular problems, such as heart attack and stroke, cancer, blood clots, serious infections and death, as compared with tumour necrosis factor (TNF) inhibitors.
  
  Based on the results of this study, a class-wide boxed warning and strengthened precautions about these risks have been added to the Australian Product Information documents for JAK inhibitors used to treat chronic inflammatory conditions: baricitinib, tofacitinib and upadacitinib.
  
  To minimise the risk of these side effects, JAK inhibitors should not be prescribed for chronic inflammatory conditions in people with a history of cardiovascular disease (e.g., heart attack or stroke), at increased risk of cardiovascular problems (e.g., current or past long-time smokers), at increased risk of cancer, and aged 65 years and over unless there are no suitable alternative treatments.
   
• Elasomeran (Spikevax) now has full approval for active immunisation to prevent coronavirus disease 2019 (COVID‑19) caused by SARS‑CoV‑2 in individuals 6 years of age and older.
   
• Ibrutinib (Imbruvica) is no longer indicated in patients with deletion 17p.

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.