April 2023

New Products

• Belzutifan (Welireg) is an inhibitor of hypoxia‑inducible factor 2 alpha (HIF‑2α). HIF‑2α is a transcription factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia. Under normal oxygen levels, HIF‑2α is targeted for ubiquitin‑proteasomal degradation by VHL protein. Lack of functional VHL protein results in stabilization and accumulation of HIF‑2α. Upon stabilization, HIF‑2α translocates into the nucleus and interacts with hypoxia‑inducible factor 1 beta (HIF‑1β) domains to form a transcriptional complex that induces expression of downstream genes, including genes associated with cellular proliferation, angiogenesis, and tumour growth. Belzutifan binds to HIF‑2α, and in conditions of hypoxia or impairment of VHL protein function, belzutifan blocks the HIF‑2α‑HIF‑1β interaction, leading to reduced transcription and expression of HIF‑2α target genes. Welireg is indicated for the treatment of adult patients with von Hippel‑Lindau disease who require therapy for associated renal cell carcinoma, central nervous system haemangioblastomas, or pancreatic neuroendocrine tumours, not requiring immediate surgery. Welireg tablets contain belzutifan 40 mg and are available in packs of 90.
   
• Elasomeran and davesomeran (Spikevax Bivalent Original/Omicron BA.4‑5) contains messenger RNA (mRNA) encapsulated in lipid nanoparticles. The mRNA encodes for the full‑length SARS‑CoV‑2 spike protein modified with 2 proline substitutions within the heptad repeat 1 domain (S‑2P) to stabilise the spike protein into a prefusion conformation. After intramuscular injection, cells at the injection site and the draining lymph nodes take up the lipid nanoparticle, effectively delivering the mRNA sequence into cells for translation into viral spike protein. The delivered mRNA does not enter the cellular nucleus or interact with the genome, is nonreplicating, and is expressed transiently mainly by dendritic cells and subcapsular sinus macrophages. The expressed, membrane‑bound spike protein of SARS‑CoV‑2 is then recognised by immune cells as a foreign antigen. This elicits both T‑cell and B‑cell responses to generate neutralising antibodies, which may contribute to protection against coronavirus disease 2019 (COVID‑19). Spikevax Bivalent Original/Omicron BA.4‑5 has provisional approval as a booster dose for active immunisation to prevent COVID‑19 caused by SARS‑CoV‑2 in individuals 12 years of age and older who have previously received at least a primary vaccination course against COVID‑19. Spikevax Bivalent Original/Omicron BA.4‑5 is contraindicated in individuals with known severe allergic reactions (e.g., anaphylaxis) to a previous dose of Spikevax (original) or Spikevax Bivalent Original/Omicron (BA.1). Spikevax Bivalent Original/Omicron BA.4‑5 suspension for injection contains elasomeran 25 mcg and davesomeran 25 mcg per 0.5 mL dose and is available in packs of ten 2.5 mL five dose vials or ten single use 0.5 mL prefilled syringes.
   
• Relugolix, estradiol (hemihydrate) and norethisterone acetate (Ryeqo) is a combination of a non‑peptide gonadotropin‑releasing hormone (GnRH) receptor antagonist and combined oral contraceptive. Relugolix binds to and inhibits GnRH receptors in the anterior pituitary gland. In humans, inhibition of GnRH receptors results in a dose‑dependent decrease in the release of luteinizing hormone (LH) and follicle‑stimulating hormone (FSH) from the anterior pituitary gland. As a result, circulating concentrations of LH and FSH are reduced. The reduction in FSH concentrations prevents follicular growth and development, thereby reducing the production of estrogen. Prevention of an LH surge inhibits ovulation and development of the corpus luteum, which precludes the production of progesterone. Therefore, Ryeqo provides adequate contraception when taken for at least 1 month. Ryeqo is indicated for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. Ryeqo is contraindicated in venous thromboembolic disorder, past or present (e.g. deep venous thrombosis, pulmonary embolism); arterial thromboembolic cardiovascular disease, past or present (e.g. myocardial infarction, cerebrovascular accident, ischaemic heart disease); known thrombophilic disorders (e.g. protein C, protein S or antithrombin deficiency or activated protein C resistance, including factor V Leiden); known osteoporosis; headaches with focal neurological symptoms or migraine headaches with aura; known or suspected sex steroid‑influenced malignancies (e.g. of the genital organs or the breasts); presence or history of liver tumours (benign or malignant); presence or history of severe hepatic disease as long as liver function values have not returned to normal; pregnancy or suspected pregnancy and breastfeeding; genital bleeding of unknown aetiology; and concomitant use of hormonal contraceptives. Ryeqo tablets contain relugolix 40 mg, estradiol 1 mg and norethisterone acetate 0.5 mg and are available in packs of 28.

New Indications

• Carfilzomib (Kyprolis) is now indicated for the treatment of patients with relapsed or refractory multiple myeloma who have received at least one prior therapy as part of combination therapy with dexamethasone, lenalidomide and dexamethasone, daratumumab and dexamethasone, or isatuximab and dexamethasone.
   
• Ivacaftor (Kalydeco) is now indicated for the treatment of cystic fibrosis in patients aged 4 months and older who have at least one mutation in the CFTR gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data.
   
• Nivolumab (Opdivo) is now indicated as a neoadjuvant treatment of patients with resectable non‑small cell lung carcinoma in combination with platinum‑doublet chemotherapy.
   
• Polatuzumab vedotin (Polivy), in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, is now indicated for the treatment of adult patients with previously untreated diffuse large B‑cell lymphoma.

New Contraindications

• Allopurinol (Zyloprim) is now contraindicated in children with the exception of those with hyperuricaemia secondary to malignancy or with Lesch‑Nyhan syndrome.
   
• Gestodene and ethinylestradiol (Minulet) is now contraindicated with concomitant glecaprevir and pibrentasvir.
   
• Lercanidipine hydrochloride and enalapril maleate (Zan‑Extra) is now contraindicated in patients undergoing dialysis; left ventricular outflow tract obstruction; untreated congestive cardiac failure; unstable angina pectoris; recent (within 1 month) myocardial infarction; and with concomitant aliskiren‑containing products in patients with diabetes mellitus or GFR < 60 mL/min, strong CYP3A4 inhibitors, grapefruit or grapefruit juice, and sacubitril + valsartan (enalapril must not be initiated earlier than 36 hours after the last dose of sacubitril + valsartan).
   
• Levonorgestrel and ethinylestradiol (Triphasil) is now contraindicated with concomitant glecaprevir and pibrentasvir.
   
• Norethisterone and ethinylestradiol (Brevinor, Brevinor‑1) is now contraindicated with concomitant glecaprevir and pibrentasvir.
   
• Somatrogon (Ngenla) is now contraindicated in patients with active tumours.
   
• Susoctocog alfa (Obizur) is now contraindicated in congenital haemophilia A with inhibitors.
   
• Trimethoprim and sulfamethoxazole (Septrin Sugar Free Oral Liquid) is now contraindicated in patients with a history of drug‑induced immune thrombocytopenia with use of trimethoprim and/or sulphonamides; and in patients with acute porphyria.

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.