Ertugliflozin is the latest sodium-glucose co-transporter-2 (SGLT-2) inhibitor available in Australia. This medication helps to regulate blood glucose levels in type 2 diabetes by increasing urinary glucose excretion.
The following products containing ertugliflozin were added to the Pharmaceutical Benefits Scheme (PBS) on the 1st December 2018:
- Ertugliflozin (Steglatro®);
- Ertugliflozin + metformin (Segluromet®); and
- Ertugliflozin + sitagliptin (Steglujan®).
A randomised study assessing the safety and efficacy of ertugliflozin in patients with type 2 diabetes demonstrated significant improvements in glycaemic control at week 26. Patients receiving 5mg or 15mg ertugliflozin as monotherapy achieved a reduction in HbA1c (%) of 0.79 and 0.96 respectively, compared to an increase of 0.20 in the placebo group. Ertugliflozin is not PBS approved for monotherapy.
One of the most common adverse effects reported with ertugliflozin therapy are fungal infections of the genital tract. Ketoacidosis, including life-threatening cases, has been identified in patients taking other SGLT-2 inhibitors. Factors that may predispose a patient to ketoacidosis include insulin dose reduction, acute febrile illness, reduced caloric intake, and alcohol abuse. Like other medicines in this class, consideration may be given to withholding ertugliflozin in situations that increase the risk of ketoacidosis such as fasting prior to surgery.
While patients undergoing anaesthesia in Australia continue to enjoy good clinical outcomes, anaesthesia-related anaphylaxis remains a significant cause of morbidity and mortality. Neuromuscular blocking agents (NMBAs) are the most commonly implicated drug class, involved in 62% of reported IgE-mediated anaphylaxis events during anaesthesia. However, up to 50% of these cases occur upon initial exposure to an NMBA. There is also marked geographical variation in the rate of these events, suggesting that an alternative agent may be inducing sensitisation.
The quaternary ammonium ion is the allergenic portion of an NMBA. This chemical group can also be found in a number of medications and household chemicals. Epidemiological studies suggest that pholcodine, in particular, may be a significant contributor to NMBA sensitisation.
Pholcodine is a cough suppressant that can be found in numerous cough liquids and cough lozenges. This medication can induce production of IgE antibodies specific for the quaternary ammonium ion. While antibody titres fall within two years of pholcodine use, re-exposure can result in dramatic increases in levels. There are often no obvious clinical signs that sensitisation has occurred, making it unlikely to be detected unless serological assays are performed. However, the presence of these antibodies may increase the risk of anaphylaxis up to 300-fold.
While a causal link between the use of pholcodine and NMBA-related anaphylaxis has not been proven, the following points may warrant consideration:
- While rare, the mortality rate for NMBA-related anaphylaxis is significant at around 4%, an additional 2% of patients suffer long-term brain injury;
- The rate of NMBA-related anaphylaxis has reduced in countries following the withdrawal of pholcodine from the market;
- Evidence supporting the efficacy of pholcodine is limited; and
- Therapeutic alternatives exist.
