Tafamidis

1. INDICATIONS AND USAGE VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. VYNDAQEL and VYNDAMAX are transthyretin stabilizers indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.

Tafamidis is a selective stabilizer of TTR. Tafamidis binds to TTR at the thyroxine binding sites, stabilizing the tetramer and slowing dissociation into monomers, the rate-limiting step in the amyloidogenic process.

2. DOSAGE AND ADMINISTRATION The recommended dosage is either: • VYNDAQEL 80 mg orally once daily, or • VYNDAMAX 61 mg orally once daily. • VYNDAMAX and VYNDAQEL are not substitutable on a per mg basis.

4. CONTRAINDICATIONS None. None.

6. ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data reflect exposure of 377 ATTR-CM patients to 20 mg or 80 mg (administered as four 20-mg capsules) of VYNDAQEL administered daily for an average of 24.5 months (ranging from 1 day to 111 months). Adverse events were assessed from ATTR-CM clinical trials with VYNDAQEL, primarily a 30-month placebo-controlled trial. The frequency of adverse events in patients treated with VYNDAQEL 20 mg (n=88) or 80 mg (n=176, administered as four 20-mg capsules) was similar to that with placebo (n=177).

7. DRUG INTERACTIONS BCRP Substrates Tafamidis inhibits breast cancer resistant protein (BCRP) in humans. Coadministration of tafamidis and drugs that are BCRP substrates may increase the exposure of substrates of this transporter (e.g., methotrexate, rosuvastatin, imatinib) and the risk of the substrate-related toxicities. Monitor for signs of BCRP substrate-related toxicities and modify dosage of the substrate if appropriate.

Store VYNDAQEL and VYNDAMAX at controlled room temperature 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).