Tafamidis on the PBS

Tafamidis is now available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of wild-type or hereditary transthyretin amyloid cardiomyopathy (ATTR-CM). This condition is associated with the accumulation of misfolded transthyretin in the myocardium, which can lead to cardiomyopathy and heart failure.

Tafamidis selectively binds to thyroxine-binding sites on transthyretin. This stabilises the transthyretin tetramer and prevents it from dissociating into unstable monomers, the rate-limiting step in amyloid formation. While no studies have been conducted to determine its direct effect on cardiac amyloid deposition, tafamidis demonstrates improved survival in patients with ATTR-CM. Compared to placebo, tafamidis is also associated with a reduced risk of cardiovascular-related hospitalisation and an attenuated decline in left ventricular systolic and diastolic function.

Treatment-emergent adverse events reported in trials include asthenia, balance disorder, sinusitis, and cataracts. Reduced serum concentrations of total thyroxine are commonly seen, although this is not accompanied by clinical signs of thyroid dysfunction. This may occur due to tafamidis displacing thyroxine from transthyretin, which normally functions as a carrier protein for thyroxine.

Tafamidis is usually administered once a day, and the capsules may be taken with or without food. Tafamidis does not significantly affect the cytochrome P450 system but does inhibit the efflux transporter, breast cancer-resistant protein (BCRP). Tafamidis may increase systemic exposure to medicines that are substrates of BCRP (e.g. methotrexate, rosuvastatin, imatinib). Patients should be monitored for potential substrate-related toxicities, and dose modification of the interacting medicine may be required.