From the Guidelines
Tafamidis should be dosed at 61 mg once daily for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in adults, as this is the FDA-approved dose for the new formulation. This dosing regimen has been shown to improve cardiovascular outcomes in ATTR-CM, including reduced all-cause mortality and cardiovascular-related hospitalization, as demonstrated in the ATTR-ACT clinical trial 1. The medication works by binding to the thyroxin-binding site of TTR, preventing its dissociation into monomers that can misfold and form amyloid fibrils.
Key Considerations
- Tafamidis is expected to have greater benefit when administered early in the disease course, as it prevents but does not reverse amyloid deposition 1.
- Patients with NYHA class I to III symptoms are likely to benefit from tafamidis, while those with class IV symptoms, severe aortic stenosis, or impaired renal function (eGFR <25 mL/min/1.73 m² body surface area) may not derive benefit from the medication 1.
- The medication should be taken with food to enhance absorption, and no dose adjustment is required for elderly patients or those with mild to moderate renal or hepatic impairment.
Mechanism and Side Effects
- Tafamidis stabilizes the transthyretin protein, preventing its dissociation into monomers that can misfold and form amyloid fibrils, which helps slow the progression of the disease by reducing amyloid deposition in the heart 1.
- Common side effects include peripheral edema, diarrhea, and urinary tract infections, but the medication is generally well-tolerated compared to placebo.
Clinical Evidence
- The ATTR-ACT clinical trial demonstrated that tafamidis had lower all-cause mortality (29.5% versus 42.9%) and lower cardiovascular-related hospitalization (0.48 versus 0.70 per year) after 30 months, compared to placebo 1.
From the FDA Drug Label
The TTR stabilization assay quantifies immunoturbidimetric measurement of the stable TTR tetramer in plasma pre- and post-treatment with 2-day in vitro denaturation with urea Using this proprietary assay, a dose-dependent trend for greater TTR tetramer stabilization is observed for VYNDAQEL 80-mg compared to VYNDAQEL 20-mg. Tafamidis exposure increases proportionally over single (up to 480 mg) or multiple (up to 80 mg) (1 to 6 times the approved recommended dosage) once daily dosing.
The dosing for Tafamidis is 80 mg once daily, as indicated by the dose-dependent trend for greater TTR tetramer stabilization observed with VYNDAQEL 80-mg compared to VYNDAQEL 20-mg 2.
From the Research
Tafamidis Dosing Information
- Tafamidis is administered orally once daily, with approved dosages including 20mg and 80mg formulations 3, 4, 5, 6.
- The 80mg dose is approved in several countries for the treatment of adults with early-stage symptomatic transthyretin amyloidosis (ATTR) polyneuropathy and transthyretin amyloid cardiomyopathy (ATTR-CM) 3, 4, 6.
- A study comparing the bioequivalence of tafamidis 61-mg free acid capsules and tafamidis meglumine 4 × 20-mg capsules found that both formulations had an acceptable safety and tolerability profile 3.
- The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and its long-term extension study found that tafamidis 80mg and 20mg doses effectively reduced mortality and cardiovascular-related hospitalizations in patients with ATTR-CM, with the 80mg dose showing a greater survival benefit 4.
Dosage Comparison
- A comparison of tafamidis 80mg and 20mg doses in the ATTR-ACT study found that the 80mg dose was associated with a significant reduction in all-cause mortality and cardiovascular-related hospitalizations compared to the 20mg dose 4.
- The study also found that the incidence of adverse events was comparable between the two doses, with no dose-related safety concerns 4.
Clinical Applications
- Tafamidis has been shown to be effective in delaying disease progression and conferring survival benefits in patients with stage 1 ATTR polyneuropathy, with up to 10 years of experience supporting its long-term effectiveness and safety 5.
- Tafamidis has also been found to be safe and tolerable in patients with acquired amyloid neuropathy, with a post-authorization study showing promise for its use in this patient population 7.